Endeavour was headed home Monday after completing its final mission to the International Space Station, dpa reported.
After undocking at 0355 GMT, the shuttle is to loop around the station, snapping photos. It is to then conduct a test in which it briefly flies a rendezvous manoeuvre with the station to test sensors designed to help dock next-generation spacecraft being developed by the US space agency.
The shuttle is to land Wednesday at Kennedy Space Centre in Florida after a 16-day mission, which is the last for Endeavour and the penultimate flight of the ageing shuttle fleet.
It delivered a high-tech particle detector to the space station that scientists hope could provide clues to the formation of the universe. The 2-billion-dollar particle physics detector, known as the Alpha Magnetic Spectrometer-2, is to allow scientists to measure cosmic rays in the search for dark matter and antimatter.
Endeavour's crew also conducted the final spacewalks by a shuttle crew.
One more shuttle flight is planned: Atlantis is to fly to the station in July.
The shuttle is the only craft large enough to bring bulky cargo such as major parts to the station although Russian, European and Japanese vehicles can bring smaller payloads.
The shuttle fleet is being retired after 30 history-making years as the US space agency focuses on developing a long-range vehicle for travel to Mars and other distant destinations.
NASA hopes to contract with commercial spaceflight providers to conduct short missions to the space station. While those craft are being developed, astronauts are to rely on the Russian Soyuz craft.
Endeavour entered service in 1992 with a mission to relaunch a communications satellite. It conducted the first servicing mission of the Hubble Space Telescope in 1993 and delivered the first US module to the space station in 1998.
After flying nearly 161 million kilometres and spending 294 days in space, Endeavour would be sent to the California Science Center museum in Los Angeles.