April (Sarah Drew) won the role in the season finale but will now have to deal with her colleagues who were also hoping to get the job.
"She's going to have her hands full," Rhimes told TV Line.
"She's not prepared to be Chief Resident, and she might find it to be much more difficult than she expected. It's going to be a long road."
Chyler Leigh, who plays Lexie, suggested that April will have a "rough time" when the show returns.
"But between Lexie and Jackson, she might have a couple of compadres on her side," she added.
Grey's Anatomy will return for a new season on September 22 at 9/8c on ABC.