The 52-year-old "Original Kings of Comedy" star also criticised the decision to give her the Arthur Ashe Courage Award at the 2015 ESPYs for going public with her gender transformation journey, reported Us magazine.
"(Arthur Ashe) fought AIDS with dignity and Honor and Caitlyn Jenner put on a dress. I don't think it's the same thing. I don't think that would have been my choice but I'm not on the ESPYS. I think Arthur Ashe and Caitlyn Jenner have little in common," Hughley said.
"This week we had the media telling us that Caitlyn Jenner was beautiful and that Serena Williams looked like a man. That was a little weird to me. The man looks like a woman and the woman looks like a man? That's ridiculous.
"I think Serena is one of the most beautiful things I've ever seen on a tennis court and Bruce Jenner looks like every PE teacher I've ever had," he added.
Hughley also tweeted side-by-side photos of Jenner, 65, and Mrs Doubtfire, played by the late Robin Williams in 1993 film.
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