The Ghana-born speedster suffered a series of injuries to his knee and Achilles, resulting in only two appearances in the last two seasons for French club La Rochelle.
On Tuesday, the club released a statement announcing that the seven-time Springbok has been "medically forced to end his career".
"I had to do this," said the 32-year-old in a video released by his club.
"I haven't really been on the pitch for two years. I'm a competitor. For me, being in a team means making a difference. So it was better for me to say stop."
Rhule first plied his trade at the Cheetahs, where he would be picked for the South African U20 side in 2012. He made his Bok debut in 2017, but fell out of favour as new management came in. Rhule went to pastures anew at Grenoble in France in 2018 and sizzling form earned him a contract at La Rochelle in 2020.
Since, the backline maestro notched up over 80 caps and bagged two Champions Cup titles with the French giants.
"I've created a lot of relationships with a lot of guys here, and even others who have already left," added Rhule.
"We've managed to do something special, and I think that will bring us closer together for the rest of our lives. It's a special club. When you arrive here, no matter where you come from, no matter what team you played for, you're a Rochelais. Thanks to all the supporters!"
La Rochelle coach Ronan O'Gara felt a deep sense of loss at Rhule's premature departure.
"He is a boy that we chose while he was playing in Grenoble, who worked hard to progress and perform with us," said the Irishman.
"He gave a lot of energy to the group and it is a huge loss for the locker room. In the final, in Marseille, he achieved something exceptional on what was far from being the best try opportunity. It allowed us to believe in ourselves. It was really a privilege to train him."