Leonardo has chosen Dejan Stankovic and Diego Milito for his Inter debut, as Ezequiel Lavezzi returns to the starting XI for Napoli.
The new Coach was appointed on Christmas Eve after a parting of the ways with Rafa Benitez and makes his first appearance on the bench at 19.45 UK time.
He has to do without Wesley Sneijder, Coutinho, Walter Samuel, Julio Cesar and the suspended Samuel Eto'o.
Leo has adopted a 4-3-1-2 system with Stankovic in the trequartista role behind strikers Goran Pandev and Milito.
Thiago Motta joins Esteban Cambiasso and Javier Zanetti in midfield, placing Cristian Chivu at left-back.
Napoli have the chance to consolidate second place by themselves and welcome back Lavezzi from his injury lay-off.
The Argentine starts at San Siro with Edinson Cavani and Marek Hamsik, while Andrea Dossena also has his chance to shine.
Hugo Campagnaro gets the nod in defence rather than Gianluca Grava in a more attacking choice.
Inter: 12 Castellazzi; 13 Maicon, 6 Lucio, 2 Cordoba, 26 Chivu; 4 Zanetti, 19 Cambiasso, 8 Thiago Motta; 5 Stankovic; 27 Pandev, 22 Milito
Inter bench: 21 Orlandoni, 11 Muntari, 15 Ranocchia, 17 Mariga, 23 Materazzi, 39 Santon, 88 Biabiany
Napoli: 26 De Sanctis; 14 Campagnaro, 28 Cannavaro, 6 Aronica; 11 Maggio, 23 Gargano, 5 Pazienza, 8 Dossena; 17 Hamsik, 22 Lavezzi; 7 Cavani
Napoli bench: 1 Iezzo, 2 Grava, 12 Dumitru, 13 Santacroce, 18 Zuniga, 21 Yebda, 77 Sosa