The 33-year-old rapper took to Twitter to admit he felt "defenceless" and that he was "done", prompting speculation he is planning to retire.
In a series of tweets, he wrote: "I am now defenseless and mentally defeated & I leave gracefully and thankful I luh my fanz but I'm dun
"ain't lookin for sympathy, just serenity ... I'm good y'all don't trip (sic)."
The news comes after the 'Forever' rapper walked off stage halfway through a show in Milan earlier this year, something which was originally thought to be down to frustration at an unresponsive crowd, although the singer's team later claimed that technical issues were at fault.
The star has also been involved in disputes with his record label Cash Money.
Following the tweets, fellow musicians have rallied to support the rapper, with many tweeting kind words of encouragement.
Missy Elliot, 45, tweeted: "@LilTunechi Prayers up 4 whatever u may be enduring right now this to will pass & may u find PEACE I will always be a fan of your work (sic)."
Chance The Rapper - who worked with Lil Wayne on the track 'No Problem' - said he was "encouraged" by his words.
He said: "Be Encouraged. Dear @LilTunechi I just wanna remind you that absolutely nothing and no one in this world can defeat you. Tell them devils back back. (sic)."
Meanwhile, Flying Lotus said that Lil Wayne was his inspiration, writing: "U put in so much work. Inspired so many. I will always be grateful for the impression u left on me a a kid. (sic)."