Rooney was named on the bench for United's Champions League defeat to Real Madrid on Tuesday, sparking speculation the 27-year-old could be on his way out of Old Trafford at the end of the season.
The England international was reportedly a target for City in 2010, when the player publicly expressed his concern over United's ambition and long-term prospects.
Mancini, however, believes the striker will not be affected by the decision to leave him out of the starting line-up and an exit is unlikely.
"I think that Rooney is one of the best strikers in Europe but I think it is difficult he can leave Manchester United," Mancini told reporters.
"I don't know," he said when asked if Rooney could be lured away.
"I don't know this situation. I can understand maybe Rooney would be upset if he didn't play but these are things that can happen in every team. After one week it is finished."
Reports have suggested centre-forward Eden Dzeko's future at City could determine a possible bid for Rooney.
The former Wolfsburg star had been linked with a move to Borussia Dortmund, but the Bundesliga champions this week dismissed those claims.
"At the moment, there is nothing. In the end, maybe, I don't know. In the summer, it could be possible," Mancini said, referring to the potential sale of the Bosnia international.
"Dzeko player is an important player for us. We want that he stays here."