Space shuttle Endeavour has blasted off for what will be its final trip into space and NASA's next to last manned shuttle mission.

Endeavour lifted off from the Kennedy Space Center at 8:56 a.m. ET into a lightly clouded sky on its way to the International Space Station, as 45,000 NASA guests watched, and tens of thousands more watched from outside the space centre's gates.

Commmanding the mission is Mark Kelly, the astronaut husband of wounded Arizona Rep. Gabrielle Giffords.

Giffords, who has been recovering in Houston from a gunshot wound to the head, was at the Cape Canaveral, Florida, space centre to watch the launch, sequestered away from the crowds and reporters for her own private viewing.

Ahead of liftoff, the six crewmembers headed to the launch pad, waving and shaking their fists in the air. Astronaut Mike Fincke took to Twitter to document his excitement about the liftoff.

"Took my last shower for a few weeks," his tweet read. "The flight docs gave a good look-over. My only issue: too much boyish enthusiasm. (no known cure)."

Added pilot Gregory Johnson in his own Twitter update: "I am really excited and charged up for this mission! Slept great."

This 16-day mission will be the next-to-last flight of NASA's space shuttle era, as the agency prepares to wind down its 30-year-old manned space exploration. The final shuttle mission will see shuttle Atlantis blast off in July.

NASA is retiring its three remaining shuttles so it can concentrate on interplanetary travel. It wants to hand over the business of getting crews and cargo to the space station to private companies.

At least one company, Space Exploration Technologies Corp., has already said it can get astronauts to the space station within three years of receiving NASA approval.

For this mission, Endeavour will head to the International Space Station, where the shuttle's all-male crew will deliver and install a US$2-billion particle physics experiment.

"It's called the Alpha Magnetic Spectrometer," space educator Randy Attwood told CTV's Canada AM Monday ahead of the launch.

"It's a telescope that doesn't look like any telescope you've seen before. It's mainly made of magnets. It's about 15,000 lbs of instrumentation that can find antimatter, dark matter – some of these bizarre things that astronomers are trying to figure out in the universe right now."

Endeavour's Canadarm will play an important role in this mission, Attwood says, who notes that the so-called "remote manipulator unit" will pick up the spectrometer and hand it to the space station arm, which will place it on top of the space station.

"We just couldn't do any of this without this robotic help," he said.

Before Endeavour is retired to a museum, the Canadian Space Agency will look to take back the shuttle's Canadarm, to place the arm into the Air and Space Museum in Ottawa.

NASA has received five Canadarms or so-called ‘remote manipulator units," over the years, though one was destroyed in the Challenger disaster in January 1986 that killed seven astronauts.

The CSA says since the arm on Endeavour has most of the components from the original arm, it is the one that it would like returned.