McLeod, who has missed the last month through injury, ruled himself out of the game against St Kilda at AAMI stadium on Saturday and says his AFL career is over.
"I'm not confident that my knee is up to playing this week, let alone get through the game," the three-time club champion said on Monday.
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"I haven't been able to train properly for a long time.
"A new era has also started at the club and I don't want to stop a younger player from playing on Saturday."
McLeod's last game for Adelaide was the upset win against Geelong in round 16.
The 33-year-old has missed the past four games after having knee surgery before the mid-season break.
Coach Neil Craig said McLeod deserved to be remembered as one of the AFL greats.
"His record is outstanding," Craig said.
"His ability to play high quality football at the top level for so long has been remarkable.
"Great players make their mark on the biggest stage and he certainly did that."
McLeod joins captain Simon Goodwin and fellow veterans Brett Burton and Tyson Edwards on the list of Adelaide retirees this season.
