"I have decided to present my resignation," Mato said in a statement yesterday, adding that she was stepping down for the good of the government and the ruling Popular Party.
Mato has not been named as an official suspect in the corruption probe, but a judge said earlier yesterday that she had "benefited from" holidays, cash payments and other gifts when she was married to Jesus Sepulveda, a former Popular Party mayor of a Madrid suburb.
The judge investigating the case said he had evidence to try 43 people for corruption, including Sepulveda and three former treasurers of the Popular Party.
Mato is one of the least popular members of Prime Minister Mariano Rajoy's government.
She was harshly criticised for her handling of the case of a Spanish nurse who became infected with Ebola after caring for two elderly missionaries who died from the disease at a Madrid hospital.
Corruption is the biggest concern for Spaniards after unemployment, according to a recent poll by the Centre for Sociological Investigations.
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