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In a statement Chambliss slammed "legislative gridlock and partisan posturing," saying he does not see the climate on Capitol Hill improving any time soon.
"This is about frustration, both at a lack of leadership from the White House and at the dearth of meaningful action from Congress, especially on issues that are the foundation of our nation's economic health," the senator wrote. "The debt-ceiling debacle of 2011 and the recent fiscal-cliff vote showed Congress at its worst and, sadly, I don't see the legislative gridlock and partisan posturing improving anytime soon."
Chambliss would likely have faced a tough primary challenge in 2014.
During the recent standoff over the fiscal cliff, he famously was one of the few Republicans who spoke publicly about believing that his hands were not tied by anti-tax crusader Grover Norquist tax pledge.
Tea Party Express Chair Amy Kremer targeted Chambliss on CNN after his vote in favor of the fiscal cliff deal.
"It's unacceptable to have somebody who votes with the Democrats more than they do with the conservatives, and he has proven time and time again he is all about the spending," Kremer told CNN earlier this month. " We're a red state, we deserve a conservative senator."
Polling groups had already begun to examine Chambliss' chances in 2014 before the end of 2012, with one group claiming he would be "very vulnerable" to hypothetical primary challengers like Herman Cain.
The Democratic Senatorial Campaign Committee released an optimistic statement in light of Chambliss' stepping down.
SOURCE: Sarah Parnass and Sunlen Miller