United and Rovers have agreed a loan deal for the 22-year-old striker until 31 December.
Macheda scored three goals in five appearances in his first spell on loan at the Keepmoat Stadium this season.
The striker returned to United after having suffered a hamstring injury, but he is now fit to return to Doncaster.
“I am delighted I have been able to convince Kiko to re-join us as it will add to our attacking options,” Doncaster manager Paul Dickov told the club’s official website.
“I would like to thank Manchester United and Kiko for choosing to come back here. I know that he was happy here and knows the set up well. His club and we were happy about his performances in the five games he appeared in, with a tally of 3 goals.
“I’m pleased the owners have allowed me to bolster our attack by bringing a quality proven striker into the squad.”