Once one of the brightest young players in the South African game, Willemse rose to prominence in 2003 when he was voted Player of the Year, Most Promising Player of the Year and Players' Player of the Year by SA Rugby.
Injury badly affected his progress during the middle years of his career but he was still recognised as one of the most dangerous runners in the Republic.
A World Cup winner with the Baby Boks in 2002, Willemse won 16 caps for his country's senior side and was a member of the 2007 World Cup squad that secured South Africa's second William Webb Ellis Trophy.
After enjoying a spell in France following the Boks' World Cup triumph, Willemse returned to South Africa with the Lions and had begun this season's Super 14 with a brace of tries on the opening weekend.
"There are no controversial issues around my decision at all," said Willemse.
"I love the team, and the guys are exceptional. It was such a breath of fresh air being able to return to the Lions after some time overseas last year and it has been so exciting.
"I have been able to play the best rugby of my career with the Lions, and I will miss each and every one of my teammates.
"The time, however, has come for me to move onto the next phase of my life."