The former San Francisco 49er superstar has unveiled the ad on Twitter.
Nike announced that Kaepernick will be a major part of its 30th anniversary "Just Do It" campaign.
The campaign featuring the former 49er reads: "Believe is something, even if it means sacrificing everything," alluding to his kneeling protest over social injustice.
A giant billboard featuring Kaepernick has been placed prominently on top of Nike's flagship just off Union Square in San Francisco.
Nike stocks rebounded a bit Wednesday morning following a dramatic dip after the announcement of the campaign.