The 29-year-old Scotland captain announced in November 2011 that he was taking an extended break from the game after being diagnosed with ulcerative colitis, a bowel condition.
He has missed most of the past two seasons, and last appeared for United's senior team on Dec. 26 2012.
He made his latest comeback in a 2-2 draw against Fulham's under-21 team on Monday.
"It's been a long time so it's good to get back tonight," Fletcher told the Manchester United television channel.
"I've been training for a few weeks now and the next progression is to get some match-time. I enjoyed it.
"The plan was to get to half-time and see how I felt. Then get to 60 minutes and take it from there and, although I felt I could have gone on a bit longer, the plan was not to play more than that so I'm better sticking to the plan and not upsetting the sports science lads."
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- Manchester United
- ulcerative colitis