The Liberal Democrat Norman Baker will step down as crime prevention minister today, after likening his experience at the Home Office to "walking through mud".
He took a parting shot at Home Secretary Theresa May, warning that "rational evidence-based policy" was in short supply at the top of her department.
In an interview with The Independent, he claims his plans had been thwarted by May and her advisers, who looked upon the Home Office as a Conservative department rather than a coalition one.
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"That mindset has framed things, which means I have had to work very much harder to get things done even where they are what the Home Secretary agrees with and where it has been helpful for the Government and the department," he said.
"There comes a point when you don't want to carry on walking through mud and you want to release yourself from that."
The Independent says his resignation is further evidence that relations are "rapidly deteriorating" within the coalition ahead of next year's general election.
It also follows an "acrimonious clash" between Baker and senior Conservatives over a three-month delay in publishing a Home Office report that found no link between tough laws and drug use, says the newspaper.
Baker, the MP for Lewes, said he was proud of his part in tackling female genital mutilation, promoting alternatives to animal experiments, bringing in a new approach to combating anti-social behaviour and championing an "evidence-based" approach to drugs policy.
He added that he had "a lot of respect" for May professionally, but said it was a pity that she viewed the Lib Dems as "almost a cuckoo in the nest rather than part of government".
Baker said he would now spend more time in his constituency, with his family and as lead singer of his band, The Reform Club, which is about to release its second album.
Diana Johnson, one of Labour's shadow Home Office ministers, said Baker's resignation was a sign of "more chaos at the Home Office" and showed that May is "losing control of her department".
