Milan have Mario Balotelli, Kaka and Mattia De Sciglio against Lazio’s Miroslav Klose, Hernanes and Antonio Candreva.
It kicks off at San Siro at 19.45 GMT, click here for a match preview.
Both sides are in dire need of a boost after recent results and protests from the supporters.
Milan are fresh from a 3-2 defeat to Parma that left them languishing in 10th place and a fan even tried to put Coach Massimiliano Allegri on eBay for €1!
Philippe Mexes is still suspended with Matias Silvestre joining Stephan El Shaarawy, Giampaolo Pazzini and Daniele Bonera on the treatment table.
Christian Abbiati is back in the squad, but the gloves are still given to Gabriel.
De Sciglio also makes his comeback from a long injury lay-off, as Kaka and Valter Birsa support Balotelli.
Lazio are without Lucas Biglia, Diego Novaretti, Senad Lulic, Giuseppe Biava, Abdoulay Konko and banned Stefano Mauri.
Cristian Ledesma, Hernanes and Klose are back in the starting XI, the German having made his comeback in Sunday’s 2-0 win over Cagliari to score and earn a penalty.
Brayan Perea also starts in what appears to be a 4-3-3 system.
Milan are unbeaten at home to Lazio since September 1989, when Paolo Maldini scored an own goal, followed by nine draws and 14 losses.
Milan: Gabriel; Abate, Zaccardo, Zapata, De Sciglio; Montolivo, De Jong, Muntari; Birsa, Balotelli, Kaka
Lazio: Marchetti; Cavanda, Ciani, Cana, Radu; Gonzalez, Ledesma, Hernanes; Candreva, Klose, Perea