Methotrexate is a highly effective drug, so, it iswidely used for the treatment of many inflammatory andneoplastic diseases. The treatment of the patients requires a longduration which exposes the patients to the side effects of thedrug. This study is carried out to evaluate the possiblealterations resulting from the administration of methotrexate onthe liver of adult albino rat and the possible protective role offolic acid as an antagonist of methotrexate hepatotoxicity.