Alley, 58, lost 75 pounds on the commercial weight loss plan, famously going from flab to fab.
She even appeared on "Oprah" in a bikini in 2006, showing off her slimmer shape.
But now, it looks as if Alley's long personal struggle to stay thin has a painful new chapter: losing the battle to keep the weight off.
The "Cheers" star has regained 85 pounds, according to the "Oprah" Web site, and is opening up again on Thursday's "Oprah," discussing how and why it happened.
"I've let everyone down," Alley says in the "Oprah" interview.
But this doesn't happen to just celebrities like Alley -- packing the pounds back on is a common outcome for many people.
Dr. Jennifer Ashton, Early Show medical correspondent, offered some tips on Thursday for people who see themselves heading back where they started.
"You want to make sure that there's not a medical cause for weight gain; things like medications and thyroid and hormonal problems can definitely cause it," Ashton said. " ...Things like depression can be there too, so you want to see a doctor if you think you've put on a lot of weight in a short period of time or if you're not eating more to account for that increase in weight."
Ashton told Early Show co-anchor Maggie Rodriguez that if a medical condition isn't the cause of the weight gain, you should "surprise your metabolism."
"Our bodies get used to a steady state and plateau, and that's when we get lulled into this false sense of security," Ashton said. "So if you see the weight coming on again, you want to revert back to the things that work."
Ashton added that you should limit your portion size at meals, and that weight loss should be about striving for health -- not a size or a number.