Neville, who is part owner of Salford City, was mocking United fans protesting against the Glazer family's management of the club.
Replying to an initial tweet branding him an 'Glazer apologist', Neville said: "From muppets on here who think something trending or an ex player having a go will move the owners out of the club! Owners don't leave clubs unless they want to or are being hurt commercially.
"A bit of noise on here isn't going to do a jot! It's like a fly attacking an elephant!"
That post ruffled O'Kane, who responded to his former teammate: "#GlazersOut fans are trying to create awareness of what the owners are doing to Man Utd simple.
"We know they won't sell, but to do nothing and let the owners ruin this great club is not on. Calling out a few ex players for "having a go" I couldn't give a f*** what you think of me."
Neville hit back with a dig at O'Kane and suggested his unprofessionalism was why he never made the grade at Old Trafford.
"Are their 2 John O'Kanes? The one I knew that cowered at the thought of giving his all for the club and was unprofessional whilst wearing the shirt," Neville posted.
"And this one who is a Twitter warrior and represents the fans with all his heart. Can't be the same bloke surely!"
O'Kane, 44, who left United for Everton in 1998, responded: "Some make it at Utd Gaz some don't we all have different paths I've found mine now! As football wasn't for me go f*** yourself."