Heigl played Izzie for six seasons of the show but left last year in controversial circumstances when she failed to return from her maternity leave.
Chambers, whose character Alex was a love interest for Izzie, has now explained that he would like Heigl to come back before the show ends.
"Heigl is so fun," he told TV Line. "She is one of the funniest people I've ever worked with. She really is a special girl. I would love to have her back. Maybe we will before the season ends."
Chambers added that he does not think Alex will ever move on from Izzie, saying: "They were the real deal - or as much as a real deal can be on Grey's Anatomy. That was the love of his life."
Last year, Heigl explained that she does not expect Izzie to return to Grey's Anatomy as it would feel "manipulative".
Grey's Anatomy will return for a new season on September 22 on ABC.
> Justin Chambers 'sad Grey's Anatomy is closer to end than beginning'
Watch Katherine Heigl and Justin Chambers in a clip from Grey's Anatomy below: