The 17-year-old Italian was at home with a friend when the attack took place and his friend suffered minor head injuries.
The robbers, thought to be wearing balaclavas, took thousands of pounds worth of goods including a watch, jewellery and money.
Macheda, who is also known by the nickname Kiko, was not hurt in the incident and police inquiries are continuing.
A spokesman for Greater Manchester Police said: "Two men stole cash and jewellery from the victims before running out of the house. Inquiries are ongoing."
The Rome-born player joined Manchester United in September 2007 after he was lured away from Italy's Lazio as a junior player.
In April 2009, he scored the winning goal in injury time during his debut performance against Aston Villa.
Police are investigating a string of robberies against Manchester United and Liverpool players living in Cheshire.
Manchester United player Darren Fletcher was robbed in March in an estimated £250,000 raid.
His 25-year-old fiancée Hayley Grice was at home at the time and forced to identify the most expensive valuables by the knife-carrying masked robbers. The couple's two children were asleep upstairs.
A 28-year-old man was arrested.
Alex Curran, wife of the Liverpool captain Steven Gerrard, was also held at knife point in her own home as thieves stole money and jewellery.
Peter Crouch was burgled in September 2006 while he was at Liverpool, losing a car and memorabilia, while fellow Liverpool player Jermaine Pennant was also targeted.