The Glasgow back-three player has undergone two operations since fracturing a fibula during an RBS 6 Nations clash with France in February 2012, but could not recover fully.
In a statement released by his club, Lamont said: "I'm sad to be retiring from professional rugby but I've been struggling with injury for some time now and it's clear I won't be able to get back to the level I was at before."
The 30-year-old added on his Twitter account: "Well that's it folks, I'm sad to say that after 14 months and exhausting every possible avenue to recovery, I'm forced to retire from rugby.
"A big thank you to anyone who has shown me support throughout my career. I have huge gratitude for the experiences that rugby has given to me.
"The highlight being the amazing people I have had the privilege to meet along the way and consequently the lifelong friendships formed.
"There are will be many things I'm going to miss, but I've had a pretty good stint. It's now time to be set free into the real world!"
Lamont underwent surgery soon after suffering the fractured fibula, when he landed awkwardly under pressure as he contested a restart. But there were further complications and he later had another operation. The former Sale and Toulon player returned to competitive action with Dundee High in January and made his Glasgow comeback by playing almost an hour in a victory over Zebre on February 10.
That proved to be his final professional game though and he has quit seven days after his team-mates sealed a RaboDirect Pro12 play-off spot.
Lamont said: "Despite a tough time personally it's been a privilege to see the boys do so well and make such good progress this season.
"It's fantastic to have been at the club during this exciting time and I wish them all the very best for the remaining games this season."
Glasgow head coach Gregor Townsend said: "Rory has had a frustrating time with injury and everyone at the club feels for him not being able to get back to fitness.
"We were all hoping he'd make a full recovery and show what he could do in a Warriors jersey.
"I'd like to thank him for his contribution to the club over his two spells here and he goes with our very best wishes for the future."
Lamont scored 19 tries in 55 games during his first spell at Glasgow from 2004 until 2007 before moving to Sale, and then returned to Glasgow from France in December 2011.
Lamont, whose brother Sean plays for Glasgow, made his Scotland debut against Wales in 2005 and won 29 caps for his country.