Oxidative stress was induced in male albino rat by doxorubicin (DOX) treatment. This study aims to evaluate the metformin (Met) impact on the DOX induced-oxidative stress in rats. Forty male albino Wistar rats grouped under four categories: Group I served as the control group while Group II received four doses of DOX (4 mg/kg) i.p, twice a week group III: was treated with Met (250 mg/kg/day) by gavage for 14 days; group IV: was treated with DOX as in group II and with Met as in group III. All rats were killed when the experiment was over; The collection of liver tissues was done for biochemical, molecular, and histopathological investigations. According to the findings, DOX treatment significantly reduced CAT and SOD activity, however, treating DOX-injected rats with Met significantly reduced the CAT and SOD activity in the liver. GPx activity was significantly increased in the DOX-intoxicated rats, treatment of DOX-injected group with Met led to significant decrease in the GPx activity. Treatment of DOX-injected group with Met led to decrease in GST activity. DOX-injected rats that treated with Met showed a substantial increase in the levels of gene expression of CAT and SOD, however, GPx and GST gene expression were down- regulated. Met improved histologically the liver tissue of albino rat received DOX. These findings revealed the Met enhanced effect on antioxidant enzyme gene expression and the simple effect on enzyme activity.