I actually know her. She's a cousin of my friend, who is also in the business (before her, actually). If you've ever been to Hollywood, you'll realize REAL fast that actors are MUCH smaller in person. I mean, much. Melissa is short; however, once you meet her, you realize she can't be much over 175. I'm totally serious. She looks like a moderately chubby person in reality. I'm guessing she is 5'2.
I also have also regularly met Parker Posey in real life a few times. She looks 115 on the screen. When you see her, you doubt if she's over 9o. The camera is an amazing thing.
If Melissa McCarthy only weighs 215, I'm a monkey's uncle... and I'm not. I weigh 207, am 5'7" tall, and wear a real size 14 (in Hollywood I'd wear a size 10 since there is a two-size difference. Dress-makers want people in Hollywood/Beverly Hills to think they're smaller than they really are. The dress size difference is a fact, not speculation). If MM wears a size 16 in Hollywood, she wears a size 20 in real life, but even still, she's a good two sizes larger than that. She HAS to be at least a size 24 in real life (so a 20 in Hollywood), and she's over 250 pounds.
The height does make quite a difference. Melissa also seems to carry a good amount of her weight on her face, so I think saying she's over 250 is probably not accurate. Judging from plus super model Tess Munster who's 5' 4" and admits to wieghing 260, I'd guess Melissa is between 215 and 240.