Health and Human Services Secretary Tommy Thompson (search) resigned on Friday.

Thompson, 63, submitted his resignation to President Bush, and announced his departure at a Friday afternoon news conference.

"I do not tender my resignation easily. While these years have been challenging, they have been rewarding," Thompson said.

"It's been my privilege to serve the American people as secretary of this American department but after nearly 40 years in public service, 40 years as a state lawmaker, 14 years as governor [of Wisconsin] ... and four years as HHS secretary, it's time for me and my family to move on to the next chapter in our life."

Meanwhile, a senior administration official told FOX News on Friday that Bush asked Defense Secretary Donald Rumsfeld (search) to remain at the Pentagon and he agreed to stay.

Bush and Rumsfeld decided on the secretary's future during their weekly meeting on Monday. Bush feels that the defense secretary is a "strong and capable leader" who in challenging times is the "right man to lead the Defense Department," the official told FOX News.

Whether or not Rumsfeld would remain had been the last big question mark about Bush's Cabinet for his second term.

Thompson's departure, on the other hand, came as no surprise, as Thompson has indicated in the past that he would like to move on in his career to do other things.

Thompson touted a number of efforts he considered accomplishments that took place under his watch.

"We touched the third rail of politics," he said, referring to the landmark Medicare legislation that passed Congress just over a year ago.

"We turned America's attention to disease prevention," he said. "And we're waging a bold new global fight against HIV AIDS."

Thompson said Bush's global AIDS initiative was going to be the "jewel of the president's legacy."

He also referred to the shortage of flu vaccine as well as his agencies efforts to combat the SARS virus.

"We helped the world understand a mysterious disease so we could contain it," Thompson said.

HHS was among the first agencies that arrived on the scene at the World Trade Center site after the Sept. 11 attacks, he said, and noted that within 10 hours of the attacks, the agency was able to deliver drugs and other supplies to affected New Yorkers.

On the bioterrorism threat, he added, "from the day I arrived, we spoke of the need to better prepare for bioterrorism and together, we helped this nation" deal with the mysterious anthrax letters and expanded the nation's cache of smallpox vaccines. He said that over 400 million doses of the vaccine are currently stocked in inventory or in the nation's medical labs "to protect if we have to vaccinate America."

The buzz around the Beltway is that Thompson's likely successor in Health and Human Services is Mark McClellan (search). He oversees the Medicare program and is the brother of White House press secretary Scott McClellan.

"Mark McClellan has really been a utility player when it comes to health issues," said Sen. John Cornyn, R-Texas.

Thompson's resignation comes amid a huge Cabinet shuffle in the Bush administration as the president prepares to head into his second term in the White House. He is the eighth member of Bush's 15-member cabinet to step down since Election Day.

When asked about all the turnover, Cornyn said it's not unusual.

"I think it tells you that these are tough jobs — leading huge federal agencies — and they're really a meat grinder when it comes to your personal life and the burnout factor," the senator said. "I think that's what's kicking in."

The Cabinet heads who have not yet resigned are Labor Secretary Elaine Chao, Transportation Secretary Norman Mineta, Housing and Urban Development Secretary Alphonso Jackson, Interior Secretary Gale Norton, Veterans Affairs Secretary Anthony Principi and Treasury Secretary John Snow.

Snow told FOX News on Friday that whether he will stay or go is a matter to be discussed only between himself and the president.

"Let me say it is an honor to be part of this administration. I have the deepest admiration for the president and I've been very pleased to be part of this administration," he said during an interview on "Your World with Neil Cavuto."

Snow would not give a straight answer as to whether he even wants to stay on for a second term, when the president will be looking for a strong hand to shepherd his tax policies through Congress.

"Sure, I like being part of an administration that develops good, well-conceived economic policies, that articulates them forcefully, that gets them through Congress, then sees the results and we're clearly seeing results," Snow said.

Thompson's announcement comes on the same day that former New York City police Commissioner Bernard Kerik (search) was named by President Bush to be the next secretary of homeland security to replace outgoing chief Tom Ridge.