"Even if it means sacrificing everything" - a move that was seen by some as controversial.
The ad finishes with the words: "It's only insane until you do it".
Nike said a 90-second version of the ad will air mostly on TV. Shares of the company were up less than one percent in midmorning trade on Wednesday; the stock had dropped almost 4 percent at one point on Tuesday.
"In their new ad campaign, we believe Nike executives are promoting an attitude of division and disrespect toward America", said College of the Ozarks President Jerry C. Davis.
Some social media users have even posted videos and photos of them destroying their Nike-branded apparel.
"Don't ask if your dreams are insane, ask if they're insane enough", Kaepernick said in the ad.
Colin references Serena Williams and praises her as "the greatest athlete ever" - while throwing similar compliments at stars like Odell Beckham, Shaquem Griffin and the U.S. Women's National Soccer Team.
Kaepernick has since issued a complaint against the NFL and accused the team owners of conspiring against allowing him to play professional football again.
Carlson then asked Portnoy how Nike is helping the cause of civil rights if it's trying to sell expensive shoes to people who can't afford them. "At the highest level", Kaepernick says.
The Nike commercial also features clips of famous athletes doing their thing. Those rules were recently put on hold pending further discussion.