Mr Uribe has vowed to press ahead with reforms
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A third minister has quit the Colombian cabinet following a government defeat in a referendum on reform.
It was unclear whether President Alvaro Uribe had forced Housing and Environment Minister Cecilia Rodriguez to leave as part of a clean sweep.
Her departure was quickly followed by news of the resignation of the national police chief.
The young president's drive to reform the economy and crack down on leftist rebels has run into resistance.
Ms Rodriguez, who was often accused in the press of failing to get results, gave no reason for her resignation.
On 25 October, voters rejected wide-ranging reform proposals in a nationwide referendum.
Last week, Defence Minister Martha Lucia Ramirez and Interior and Justice Minister
Fernando Londono handed in their resignations.
Mr Uribe has since replaced them with close allies from the business world with limited political experience.
Mr Londono, seen as Mr Uribe's right-hand man, had caused a row by suggesting the president might cut short his term in office and
call early elections.
The president invested much of his time in promoting the referendum - which dealt with issues ranging from trimming back parliament to getting new funds to fight the drug trade and the militants - and many saw it as a vote of confidence in his administration.
The rash of political resignations has been accompanied by a series of corruption scandals which have cost the jobs of the head of police, Teodoro Campo, who resigned, and the Medellin police chief, Leonardo Gallego, who was sacked.
The BBC's Jeremy McDermott in Colombia says at the start of his administration, Mr Uribe said that his ministers would serve the full four years of his administration and that the fight against corruption was the top priority.
After just over a year of government, he says, five ministers have gone and corruption seems more prevalent than ever.