Effects of medroxyprogesterone acetate (MPA) on hepatic glucose handling and drug metabolism were investigated in female rats with intact and damaged liver. Hepatic glucose-6-phosphatase activity, glycogen content and fasting blood glucose were assessed as indices of glucose metabolism. Cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity were assayed to reflect liver drug metabolism. Liver injury was induced by dimethylnitrosamine and carbon tetrachloride. The results demonstrate that hepatic glucose handling and drug metabolism were changed in a parallel fashion in intact, damaged and induced liver. The MPA-induced changes in glucose metabolism were slight in intact animals, whereas the compound has an increasing effect on glucose and drug metabolism in rats with damaged liver. The findings demonstrate that MPA enhances the normalization of hepatic glucose and drug metabolism in damaged liver.