From June 2003 up to March 2006 the "Acquario" was closed to the public while important restructuring was carried out. The project was the work of architects Piero De Amicis and Luigi Maria Guffanti together with scientific director Mauro Mariani. The aquarium was reopened to the public on the 1st April 2006 after three years of important painstaking restoration and renovation work making the Art Nouveau edifice more capacious, modern and functional. The whole structure and visitors' itinerary among the exhibits have been completely renewed. The new project meant that available space was almost doubled. The entrance lobby is more than twice its former size and the building is now composed of three floors, where previously there were only two, by recovering and modernizing the old basement areas. The aquarium has been enlarged, made practicable and accessible to all members of the public and fitted out with new facilities: a bookshop and comfortable refreshments area which nowadays visitors to museums and cultural areas have come to expect. Stairs and lifts lead to the floor above where the administrative offices and prestigious library are situated. The latter is one of the most valuable and important in the field of marine biology and hydrobiology. An auditorium which can host meetings and congresses will once again become a centre for the many events organized by the "Acquario". Novelties on the first floor include new spaces available to the public, a winter garden in the centre of the building, a balcony looking onto Parco Sempione and the outside tanks. Particular attention has been dedicated to the settings and the realization of a suggestive bridge-shaped tank which has a strong impact on visitors. Ample spaces are dedicated to didactical areas for temporary exhibitions on specific subjects and reserved for cultural activities.

The expositive itinerary concentrating on water courses ranging from the rain and snow feeding torrents pouring down from high mountains, to the lake, to the mouth of the river Po, the lagoon environment making an ideal link with marine life in sea water tanks. Innovatory structures for Milan and evocative proposals like the reconstruction of a sunken wreck and the transparent bridge tank allowing visitors to imagine being surrounded by sea creatures above and below them. An exotic touch is represented by a large tank dedicated to the Red Sea - the tropical sea nearest Italy. Every tank is classified by the altitude with respect to sea level. Among the innovative elements are three open ponds in which the public can observe reconstructed environmental habitats and experience the sensation of being immersed without any barrier. The partially computerized operational system allows the habitats to be more closely monitored, including taking into account variations relevant to the time of the day night or season in order to guarantee optimum conditions for living organisms.