The video features imagery seemingly created to raise the USA president's ire, including Muslim and refugee athletes.
The NFL said it "embraces the role and responsibility of everyone involved with this game to promote meaningful, positive change in our communities".
Kaepernick tells viewers to "believe in something, even if it means sacrificing everything", which is a less-than-subtle hint at Kaepernick's own actions during his time in the NFL.
He said: "When I walked into the team room this morning, there were some people who were fuming".
The ad concludes with the lines, "So don't ask if your dreams are insane".
Kaepernick, a former 49ers quarterback, started a political firestorm after he began protesting for the "Black Lives Matter" movement by kneeling during the performance of the national anthem.
The now-former quarterback was announced Monday as the face of a new ad campaign to celebrate the 30th anniversary of Nike's "Just Do It" slogan.
If you have only one hand, don't just watch football.play it at the highest level.
"I think when you're a huge company like Nike, it's hard to stay edgy".
People have been on either side of the spectrum when it comes to Nike's decision.
Talking on his late-night show Noah said: "Wow!"
It wasn't long before the announcement of the ad sparked outrage among those who agreed with the president's stance that Kaepernick's knee protests during the national anthem are disrespectful toward the armed services. "As for me, I support Colin, I support my brother, I support the stance that he's taking". Kaepernick has been signed with Nike since 2011, though the company has kept quiet that he would be involved in a future campaign, according to ESPN.
Cantona posted a photograph of him wearing a Nike hoodie, with the caption "I am wearing #Nike more than ever".