"I put my heart and my soul and my body into it this year to see how it was going to feel, but my body cannot handle it anymore," Izturis said through a translator. "So, I decided this is going to be my last time playing baseball."
The 35-year-old Izturis, hindered by injuries in recent years, was in Toronto's spring training camp on a minor league contract. He had not appeared in a big league game since April 2014.
He had left knee surgery in 2014 and shoulder surgery last year.
Izturis had re-signed with the Blue Jays in January, agreeing to a deal that would have given him a $900,000, one-year contract if he was added to the 40-man roster.
A career .269 hitter, Izturis spent 11 seasons with the Montreal Expos, Los Angeles Angels and Blue Jays. He hit .300 with 65 RBIs in 114 games in 2009, helping the Angels win the AL West.
"I know one thing you can look back on is he was a winning player," Blue Jays manager John Gibbons said. "He played the game the right way. He was on a lot of those successful teams in Anaheim, and he did things right."
Izturis said he plans to continue being a part of baseball, working to help kids with his half-brother and former big league shortstop, Cesar, at his academy in his Venezuela.
For now, he hopes to spend more time with his family.
"I tried. I tried really hard," Izturis said. "Even this morning, I went to the cage and hit. I want to thank the organization for giving me the opportunity to play for the last three years. I really tried hard, but I couldn't do it anymore."
Izturis' retirement leaves New York Mets pitcher Bartolo Colon as the last active player to have suited up for the Montreal Expos. The Expos were relocated and became the Washington Nationals after the 2004 season.