In December, 1499, the Sforza family was driven out of Milan by French forces and Leonardo was forced to leave Milan and his unfinished statue of Ludovico Sforza's father, which was destroyed by French archers, who used it for target practice. Leonardo then returned to Florence in 1500.
When Leonardo returned to Florence the citizens welcomed him with open arms because of the fame he acquired while in Milan.
The work he did there strongly influenced other artists such as Sandro Botticelli and Piero di Cosimo, as well asMichelangelo and Raphael.

In 1502 Leonardo entered the service of Cesare Borgia, Duke of Romagna and son and Chief General of Pope Alexander VI. For this post he supervised work on the fortress of the papal territories in central Italy. In 1503 he was a member of a commission of artists to decide on the proper location for the David by Michelangelo.
Towards the end of the year Leonardo began to design a decoration for the Great Hall of the Palazzo Vecchio. Leonardo chose the Battle of Anghiari as the subject of the mural, a victory for Florence in a war against Pisa. He made many drawings and sketches of a cavalry battle, with tense soldiers, leaping horses and clouds of dust. In painting The Battle of Anghiari Leonardo again rejected fresco and tried an experimental technique which didn't work. Leonardo went on a trip and left the painting unfinished. When he returned he found that the paint had run; he never completed the work. (The paintings general appearance is known from Leonardo's sketches and other artists' copies of it )
During the period of time that Leonardo spent painting the Palazzo Vecchio he also painted several other works, including the most famous portrait ever, the Mona Lisa. The Mona Lisa, also known as La Gioconda.
It is assumed that Francesco di Bartolommeo di Zanobi del Giocondo, one of the noblest citizen of Florence, ordered a portrait of his third wife Lisa di Antonio Maria di Noldo Gherardini.
Leonardo started to work at this painting in 1503. At this time Mona Lisa was twenty-four year old. He worked at the portrait for the next four years.
When Leonardo left Florence in 1507 he did not sell the painting but he kept it for himself.
Several believe, that Leonardo did not hand over the painting, because it was not finished. Others believe that Leonardo loved it too much.

Leonardo da Vinci arrived with the painting in his baggage in France in the year 1516. Leonardo sold the painting in France to King Francis I., who bought it for the castle in Amboise. In the following time Mona Lisa came to Fontainbleau, Paris, Versailles and then to the collection of Louis XIV. After the revolution in France the painting got a new home in the Louvre. Napoleon took it away from there and hung it up in his bedroom. When Napoleon was banished Mona Lisa returned into the Louvre in Paris. On 21 August 1911 Mona Lisa was stolen by an italian thief, who brought the painting to Italy, where it emerged two years later in Florence. After some exhibitions the Mona Lisa returned again to Paris.
An acid attempt damaged the lower half of the painting in 1956. The restoration took several years.
In the 60's and 70's Mona Lisa was exhibited in New York, Tokyo and Moscow.
Today the painting is behind bullet-proof glass in Paris in the Louvre and international terms are prohibiting any further travel on its part.
In the painting Leonardo deplys his invented technique for establishing atmosphere 'sfumato' But of course the Mona Lisa is most famous because of the unique expression on Lisa del Gioconda's face. She appears to to have begun - or to have finished - smiling.

In 1506, Leonardo returned to Milan to finished up some of his projects that he had to abandon during his hasty departure. He stayed there until 1516 when he moved to Cloux, France, where he stayed with his pupil Melzi. While in Milan he was named Court Painter to King Louis XII of France, who was then residing in Milan. For the next six years he traveled from Milan to Florence repeatedly to look after his inheritance. In 1514 he traveled to Rome under the patronage of Pope Leo X. During this time Leonardo's energy was focused mainly on his scientific experiments.
He then moved to France to serve King Francis I. It is here in Chateau de Cloux that he died on May 2,1519
Leonardo constantly reworked his drawings, studies and mechanical theories. In Leonardo's Studies of Water Formation, the flow patterns observed are swirling around , then below as it forms a pool. Using modern slow motion cameras scientists now study the same effects that Leonardo wrote about and observed with his naked eye Another study of water and wind is his Apocalyptic Visions. This is a collected study of hurricanes and storms. In these highly detailed drawings the pen lines so carefully marked explode into action similar to the storms themselves.
Leonardo's mathematical drawings are also highly skilled. In a math formula Leonardo proved the theory of perpetual motion false but it still intrigued him. Among his vast notes was the idea for a perpetual motion machine. His ideas for completing this task involved an unbalanced wheel that would revolve forever, conserving its energy.
Another mathematical drawing was the Polyhedron. This three dimensional figure represented proportions to him "not only in numbers and measurements but also in sounds, weights, positions and in whatsoever power there may be"

In any event, contained in the Notebooks are plans and drawings for what we recognize today as the first working propeller, a submarine, a helicopter, a tank, parachutes, the cannon, perpetual motion machines, and the rope ladder. There are perfectly executed drawings of the human body, from the proportions of the full figure to dissections in the most minute detail. It was observed, however, that Leonardo's interest in the human body and his ability to invent mechanical things were actually not as paramount to him as was his fascination and awe of the natural world. For the last two years of his life he was paralysed down the right side of his body. He is not known to have ever married or had children. In fact, it was said of him that he only saw women as "reproductive mechanisms".

Leonardo lived to be 67 years old.

We have already quoted his last words. It was humble and fine for him to utter them. But he was a most truthful man, and the statement 'I have offended God and mankind because my work did not reach the quality it should have' is by far the least truthful thing Leonardo da Vinci ever said.