The 31-year-old Glenn, a first-round draft pick out of California in 1997, started 154 regular-season games during his 10-year career. A steady blocker on the left side of the offensive line, he was a main reason quarterback Peyton Manning was sacked just 15 times last season and a league-low 176 times since Manning joined the team in 1998.
"Making this decision, I had to step outside that (team) role and see what was good for myself and my family, and that was hard to do," Glenn said at a news conference at the Colts' headquarters. "Hearing people talk and players asking me to reconsider and reminding me of some of the things and what I mean to this team, it hurts. It really hurts.
"But I'm real convinced this is what I should do."
The 6-foot-5, 332-pound Glenn was second to 11-year veteran receiver Marvin Harrison in years of service with the Colts.
Glenn said the Colts' long championship season was "emotionally draining," and in early May he began feeling he was "just going through the motions" during offseason workouts.
By the end of last month, he said, he realized his passion for the sport had diminished.
"It would not be fair to the team or the game not to give it my all," he said.
Glenn, who was born in Cleveland but grew up in Oakland, Calif., said he would remain in Indianapolis and work in the community and with a nonprofit charity organization he started in 2001.
He said Manning and others tried to talk him out of retiring, but when their efforts failed, wished him well.
"That's OK," he said. "I wanted to hear what everybody else's feelings were, because it was affecting everybody. ... I hate the fact I feel like I feel, but I've just got to move on."
The Colts have lost four other starters - cornerbacks Jason David and Nick Harper, former Pro Bowl linebacker Cato June and running back Dominic Rhodes - through free agency. They also released receiver Brandon Stokley and defensive tackle Montae Reagor, starters until they suffered season-ending injuries in 2006.
"Obviously, it's hard to replace a player of Tarik's ability," team president Bill Polian said. "He hardly ever was injured, but you prepare for that as a team, so we have players that are going to have to step in."
Polian wouldn't speculate on the Indianapolis lineup as the team prepares for the start of training camp on Sunday in Terre Haute.
"We've got a lot of good players on the offensive line," he said. "Virtually any player can play any position. ... Right now, it's a question of working through all the permutations."
Team owner Jim Irsay said he met with Glenn for about three hours Monday night, but did not try to get him to change his mind.
"I just want to make sure, face to face, he was sure about this decision. ... I could tell he was. It's tough, but we're going to go forward," Irsay said.