Manganiello previously starred on the show as Owen, a love interest for Brooke (Sophia Bush).
He was last seen in season seven, when he was in the same rehab meeting as Millie (Lisa Goldstein).
Manganiello has now told Digital Spy that he would be interested in returning to One Tree Hill for the ninth season, which is expected to be its last.
"That's up to [creator] Mark [Schwahn]," he said. "I love One Tree Hill. I loved being on that show. So, I mean, that's up to Mark."
Manganiello continued: "I would love to come back. I mean, I'd be curious to see how they'd bring me back, but yeah, I'd love to go back."
Paul Johansson and Tyler Hilton have already signed up to return to One Tree Hill, while former star Chad Michael Murray has revealed that he would "definitely" return if it was possible.
Manganiello is currently starring as Alcide in True Blood, which is broadcast on Sundays at 9pm on HBO in the US. The third season will air in the UK on Channel 4 in early September.