The Paraguayan striker will stay on loan at Blackburn until the end of the season.
Santa Cruz joined City from Blackburn in a £17.5million deal in 2009, but has failed to make an impact at Eastlands.
“Roque had a fantastic time when he was first here and he showed his quality,” said Blackburn manager Steve Kean. “Hopefully he’ll do that again until the end of the season.
“It’s massive from his point of view because he doesn’t have to settle in at a new club. He’s coming back to a place that was special to him and I’m sure he’s going to deliver just as good or even better.
“We’re trying to speak to Manchester City at the moment regarding an option about signing Roque at the end of the season, so we don’t know about that yet.
“It’s something we’ll ask for, but we don’t know if they’ll commit to it.”
