Kaepernick and another former 49ers player, Eric Reid, have not been signed by any of the NFL's 32 teams since their protests spread around the league.
"Believe in something, even if it means sacrificing everything", the caption reads, followed by the hashtag #JustDoIt.
The ad is a simple black and white image of Kaepernick's face with the message, "Believe in something". The Nike swoosh accompanies the image.
Former San Francisco 49ers quarterback Colin Kaepernick has been tapped as one of the faces of Nike's 30th anniversary "Just Do It" campaign.
He continued his demonstration by kneeling during the anthem before subsequent contests, sparking a nationwide movement of athletes protesting in solidarity - which in turn drew the ire of President Donald Trump and a highly publicized counterprotest by Vice President Mike Pence. He became a free agent at the end of the season, and has remained unsigned. Kaepernick tweeted the ad from his Twitter account Monday afternoon.
Darren Rovell of ESPN is reporting that Nike has held Colin Kaepernick under contract this whole time, since they signed him to an endorsement deal at the beginning of the decade.
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Nike is the NFL's official uniform sponsor.
In May this year, the NFL announced that players who knelt for the national anthem would be fined under a new policy.
"Nike has always been and will continue to be my family's favorite shoe", wrote Twitter user @TheDionneMama.
Though not as controversial, the ad was in response to a kerfuffle over the French Open's decision to bar Williams from bringing back her popular "catsuit" outfit to the 2019 tournament.
The new Nike adverts, which were unveiled just days before the kick-off of the 2018 National Football League season, show a portrait of Kaepernick with the slogan: "Believe in something".