Bolton was unable to win confirmation by the U.S. Senate.
U.S. President George W. Bush had to use his presidential powers to appoint Bolton in August 2005, while Congress was in recess, in the face of opposition among U.S. senators who held up a vote on the nomination
But that appointment expires when the current Congress adjourns, expected within a few days.
Second Setback
Bolton’s departure is the second setback for Bush in recent weeks. U.S. Secretary of Defense Donald Rumsfeld announced his resignation the day after the November 7 elections.
Bush said in a written statement that he accepted Bolton's decision to leave with "deep regret."
The president said Bolton served as the top U.S. envoy to the United Nations with "extraordinary dedication and skill."
He praised Bolton's negotiations that resulted in unanimous Security Council resolutions regarding North Korea's military and nuclear activities and the outgoing envoy's efforts to reform how the United Nations is run.
Bolton was the U.S. administration's top official in pressing for UN reforms following revelations that the Iraq oil-for-food program was widely mismanaged.
In his written statement, Bush also took the opportunity to express disappointment at senators who prevented Bolton from receiving an up-or-down vote on his nomination.
"This stubborn obstructionism ill serves our country and discourages men and women of talent from serving their nation," Bush said.
Praise From His Colleagues
The Japanese ambassador to the United Nations, Kenzo Oshima, said in New York that he regrets Bolton's departure.
"To me, [it is] really disappointing to see Ambassador John Bolton go," Oshima said. "He has been an exceptionally skillful diplomat at the United Nations at a time when the UN faced very challenging issues like reform. And, in the Security Council, John Bolton was spearheading a number of important issues."
China's ambassador to the United Nations, Wang Guangya, also expressed regrets.
"I worked very closely with him and I believe that he is hardworking and so I regret that he is going to resign," he said. "He has pushed American interests here, so I think that this is my impression. Sometimes we differ, but certainly, I think that I can work together with him. He knows the job."
Critics say Bolton's style is confrontational and sharp. The incoming chairman of the Senate Foreign Relations Committee, Democratic Senator Joseph Biden (Delaware), said he saw "no point in considering Mr. Bolton's nomination again."
There was no immediate announcement concerning a new nominee.