President Bush appointed Bolton to the position during a congressional recess in August 2005, and his term expires at the end of the current congressional session, which could be as early as this week.
Bolton's nomination languished in the Senate Foreign Relations Committee, blocked by Democrats and moderate Republican Sen. Lincoln Chafee of Rhode Island, who lost re-election in November.
His nomination appeared headed for even more trouble with Democrats in control of the upcoming Congress.
Sen. Joseph Biden, D-Del., who will lead the Foreign Relations Committee in the 110th Congress, said he saw "no point in considering Mr. Bolton's nomination again."
President Bush said it was with "deep regret" that he accepted Bolton's resignation, reported Reuters. "I am deeply disappointed that a handful of United States senators prevented Ambassador Bolton from receiving the up or down vote he deserved in the Senate," the president said.
Critics objected to Bolton's brusque style and doubted he could bring reform to the international body.
But President Bush pointed to several of his achievements: "Ambassador Bolton led the successful negotiations that resulted in unanimous Security Council resolutions regarding North Korea's military and nuclear activities. He built consensus among our allies on the need for Iran to suspend the enrichment and reprocessing of uranium.
"His efforts to promote the cause of peace in Darfur resulted in a peacekeeping commitment by the United Nations. He made the case for United Nations reform because he cares about the institution, and wants it to become more credible and effective," the president said, according to the Associated Press.
