Investigators said Saturday the burglary happened sometime earlier in the week at Jackson's home in South Philadelphia, not far from the team's practice facility.
Police say the cash and jewelry were taken from a safe. A silver 9mm handgun was also missing.
No arrests have been made. Jackson is offering a $50,000 reward for information leading to a conviction in the burglary, The Associated Press reported. A police spokeswoman says the investigation is ongoing.
Jackson released a statement Sunday through his publicist to the Philadelphia Inquirer's Jeff McLane.
"DeSean is clearly upset that his home was burglarized while he was out of town on vacation," the statement said. "He has always felt very safe in his community, and it concerns him someone would victimize his place of residence."
The statement went on to clarify how much was taken from Jackson's home. He lost personal items, jewelry and a small amount of money, and the "large sum" taken was in items, the statement said.
Jackson was the Eagles' leading receiver this season with 82 catches for 1,332 yards and nine touchdowns. He signed a five-year, $51 million contract before the 2012 season.
The Associated Press contributed to this report.