The first lay girls’ boarding school in Florence, desired by Gino Capponi, the Institute was born in 1823 through the efforts of Grand Duke and Duchess Leopold II and Maria Anna Carolina of Saxony, and was inaugurated in 1825 with headquarters in via della Scala. From the beginning, the Grand Duke and Duchess wanted it to be a state institute and not private. It possesses a didactic physics collection (about 150 exhibits from the 19th and 20th centuries), which includes numerous instruments from the various branches of the discipline. In 1865, the Institute moved into the Medici Villa at Poggio Imperiale, where it still is today.

Confiscated from the Salviati family by Cosimo I and then sold to the Odescalchi family, the villa was purchased in 1622 by Grand Duchess Maria Maddalena of Austria, widow of Cosimo II, and renamed Poggio Imperiale in honour of the Austrian imperial house. Transformed by Giulio Parigi in the second half of the 17th century, it became the favourite site of theatrical performances, parties and receptions. In the second half of the 18th century, works for its enlargement were directed by Gaspare Maria Paoletti and, later, Pasquale Poccianti and Giuseppe Cacialli gave it a neoclassical look.

The villa is also tied to a famous episode in the history of healthcare. In 1756, Tuscany was struck by a violent epidemic of smallpox. Giovanni Targioni Tozzetti, grand-ducal physician, practised grafts of the cowpox virus on six foundlings, a practise not unanimously approved by the scientific world: the illuminated reformism of the Lorraines gave Tuscany the primacy in the battle for affirming this type of preventive medicine. Grand Duke Peter Leopold of Lorraine, too, subjected himself to vaccination: physician Angelo Gatti inoculated the Grand Duke in the Villa of Poggio Imperiale at 11 am on May 13, 1769.