The actress co-starred with the birthday boy on 'ER.'
In honor of the occasion, Margulies shared a throwback snap of her and Clooney hugging, which was taken while they were starring on the medical drama. Clooney starred as Dr. Doug Ross for five seasons, while Margulies played Carol Hathaway for six seasons.
"Happy Birthday to my dear friend who reminded me yesterday that we have known each other for 27 years!" Margulies captioned the pic. "This picture was taken for the cover of TV Guide on the back lot at WB’s studios during a lunch break."
Margulies also praised Clooney in her post, writing that he's "a stand up fellow who walks the walk and reminds me all the time that doing the right thing is always the braver choice."
During on an appearance on Thursday's Jimmy Kimmel Live, Margulies said she wrote to Clooney "yesterday because I wanted to write to him on the last day of his 50s."
"I thought it would be fun to say, Dear -- well, I call him Doug, he calls me Carol, it's something we've always done," she shared with a smile. "I said, 'On this, your last day of being 50, I just want you to know that when you're 90 and you look back and see how young 60 was, you will curse the day you wasted time thinking you're getting older, or that you're too old.'"
"I have to give credit where credit is due," she added. "George, I give him tremendous credit for helping launch my career. He happened to make a phone call and went out of his way to tell me not to take another job, because he thought they might keep me as a series regular. Because of that phone call, I ended up on E.R.
In an April interview with People, Margulies opened up about meeting Clooney on the set of E.R.
"He could not have been kinder or sweeter," she said of Clooney. "... With George and me, it was so organic. I was just supposed to be a guest star, number 39 on the call sheet. But he treated everyone the same."
As they continued to work together on the medical drama, whose cast recently reunited for a charity event, Margulies revealed that Clooney became her mentor.
"I followed and watched how he conducted himself on the set. When you create an environment that people feel safe in, then you do your best work. And George taught me that," she said. "I felt so safe with him."
As for how Clooney feels about entering a new decade, he recently told ET, "I’m not thrilled with it but it's better than dead. So I'll take it."