The Vogue singer made headlines last month with a provocative bedroom photoshoot taken in (and under) her bed.
50 Cent had reshared the snaps, including the one of her under the bed, comparing her to the Wicked Witch of the East from The Wizard of Oz, where Madonna’s legs where photoshopped under a house from film.
He added: “Starz ask me to do a remake, I said only if Madonna is gonna play the role because i need star power and sex appeal in this one.”
In another caption, he wrote: “That’s Madonna under the bed trying to do Like A Virgin at 63. She shot out, if she don’t get her old ass up.”
After his comments caught Madonna’s attention, she issued a scathing response on Instagram.
Posting on her Story, she wrote: “Here is 50 Cent pretending to be my friend. Now you have decided to talk smack about me!
“I guess your new career is getting attention by trying to humiliate others on social media, the least elevated choice you could make as an artist and an adult.
“You’re just jealous she won’t look as good as me or have as much fun when you’re my age! Too bad there are no sour grapes emojis.”
Madonna then posted a video of her with a green alien filter, where she added: “Cheer up, things could be worse, you could be me for instance. Personally, I like the way I look, but there are those that find it hard to appreciate people and things that are different.
“And they try to shame me or humiliate me or make me feel less than because I am not like everyone else.
“But in fact, I cherish my uniqueness and I’ve grown stronger because to be unique is to be rare.”
50 Cent has now issued an apology on Twitter, writing: “I must have hurt Madonna feelings, she went and dug up a old MTV photo from 03. Ok I’m sorry I did not intend to hurt your feelings.
“I don’t benefit from this in anyway I said what I thought when I saw the picture because of where I had seen it before I hope you accept my apology.”
50 Cent’s original posts no longer appear on his Instagram page.
Madonna previously called out Instagram for removing one of the photos from her photoshoot due to the fact that one of her nipples was exposed.
She fumed: “It is still astounding to me that we live in a culture that allows every inch of a woman’s body to be shown except a nipple. As if that is the only part of a woman’s anatomy that could be sexualised. The nipple that nourishes the baby!
“Can’t a mans nipple be experienced as erotic??!! And what about a woman’s ass which is never censored anywhere.”