Patrice Evra, Rio Ferdinand, Tom Cleverley and Danny Welbeck all come into the side following the team's win over West Ham United at the weekend, while Shinji Kagawa and Javier Hernandez are among those named on the bench.
Meanwhile, there are also four changes for the visitors, as they aim to keep the pressure on league leaders Chelsea.
Man Utd: De Gea, Rafael, Ferdinand, Jones, Evra, Carrick, Cleverley, Fellaini, Mata, Welbeck, Rooney
Subs: Lindegaard, Buttner, Fletcher, Kagawa, Young, Valencia, Hernandez
Man City: Hart, Zabaleta, Kompany, Demichelis, Clichy, Toure, Fernandinho, Nasri, Silva, Navas, Dzeko
Subs: Pantilimon, Kolarov, Lescott, Milner, Garcia, Negredo, Jovetic
You can follow live coverage of the derby at Old Trafford with Sports Mole this evening.