The team placed Perez on the disabled list Saturday -- retroactive to June 1 -- with patella tendinitis in his right knee.
The move ended an ugly standoff with the left-hander that has dragged on for weeks.
The team said Perez arrived at Citi Field on Friday complaining of discomfort in his right knee -- the same knee that required surgery on Sept. 1, 2009.
He was seen by team doctor Struan Coleman before Friday night's game and underwent an MRI exam at the Hospital For Special Surgery that night. He is expected to leave for Florida on Saturday to begin his rehab.
The Mets had been trying to send Perez down to the minor leagues for weeks, but the lefty refused, as is his right under the collective bargaining agreement.
Perez, in the second year of a three-year, $36 million contract, had been banished to the bullpen earlier this month because of his ineffective and inconsistent performances as a starter. The team had asked him to accept a demotion to the minor leagues, but Perez, who had the right to refuse the assignment because he's played at least five seasons in the big leagues, chose instead to stay with the Mets and pitch out of the bullpen.
There was plenty of skepticism surrounding the timing of Perez's injury because the Mets needed to make a roster move Saturday to make room for lefthander Jonathon Niese -- who will start today against the Marlins. Niese is making his first start since suffering a hamstring injury May 16.
In placing Perez (0-3, 6.82 ERA) on the DL, the Mets avoided having to send down a reliever, such as Jenrry Mejia, to create space for Niese.
Manuel said Perez, 28, told him that the discomfort in his knee first started after a May 31 outing in San Diego.
"He never felt any discomfort in his knee, other than when I came in yesterday," Manuel said.
The manager was asked if he thought it was possible Perez was pitching hurt all season.
"I thought that with the velocity not ever getting to what I saw in 2008, that always concerns me to some degree," he said. "But the athlete tells you that he's fine, he's fine, doesn't feel anything, you have to give him the benefit of the doubt."
Both Manuel and assistant GM John Ricco said Perez will work as a starter in Florida once he is healthy enough to throw.
"He says he's not able to pitch the way it is right now," Ricco said. "When a player tells you he's injured and a doctor confirms that, from where I sit, that's what the DL is for."
Both Ricco and Manuel believe Perez will return to the team as a starter. Perez last started on May 7, when he allowed seven earned runs (four homers) in 3 1/3 innings in a 7-2 loss to the Marlins.
"I see him going down and trying to find his stuff as a starter," Manuel said. "How we use him would be determined on how it would fit for us when he gets back."
There is no timetable for Perez's return. He can remain on the 15-day disabled list indefinitely. The Mets would have to decide on activating Perez 30 days after his first rehabilitation appearance in a sanctioned game.
Ian Begley is a contributor to ESPNNewYork.com. Information from The Associated Press contributed to this report.