A plane carrying Clinton and her aides took off from Andrews Air Force Base outside Washington at about 00:15 am (0515 GMT).

The chief U.S. diplomat was to give a speech in Berlin yesterday before joining German Chancelor Angela Merkel and other world leaders in celebrations today for the 20th anniversary of the fall of the Berlin Wall.

In a preview of her visit, Clinton told a Washington audience on Friday that the wall's fall marked the end of a Cold War era in which the world was divided into clear blocs.

"So we find ourselves now in a much more complex world, and we just have to be up for it and we have to be smarter about it," Clinton said. "And we have to demand more from ourselves and our partners."

President Barack Obama's adminstration, despite the adulation he enjoys in western Europe after the departure of his predecessor George W. Bush, is struggling to obtain more support from European partners in Afghanistan.

Clinton's visit comes as the Obama administration pursues a weeks-long internal debate about a new strategy for Afghanistan, where Taliban rebels are gaining ground.

A senior State Department official told reporter on condition of anonymity that Afghanistan will be a key topic when Clinton meets Merkel, her foreign minister Guido Westerwelle and counterparts from other European nations.

It is a main issue "because again we are looking to coordinate closely with our allies to try to help figure out the best way forward, that all of can contribute to stabilizing Afghanistan," the official said.

Germany, which has 4,200 troops in Afghanistan, has come under fire from its allies for refusing combat missions there.

Clinton, the U.S. official said, will also pursue multilateral diplomatic efforts to curb Iran's and North Korea's nuclear ambitions during her stop in Berlin as well as her visit to Singapore and China afterward.

The United States, Russia, China, Britain, France and Germany are partners in negotiations with Iran aimed at halting Tehran's uranium enrichment program - which western countries fear masks efforts to build a bomb.