Cadmium (Cd) is an environmental cumulative pollutant affects many organs specially liver. Recently, plants possessing medicinal activities are investigated in mitigating hepatotoxicity. Pomegranate fruit has been intensively utilized as natural remedy in many cultures. The effect of methanolic extract of pomegranate peels (PEE) against cadmium hepatotoxicity in mice is evaluated. Forty mice were used in this study. Animals were divided into four groups, the 1st control group was given saline solution, the 2nd group was orally treated with 50 mg/kg/b.w. of methanolic pomegranate peels extract (PPE), the 3rd group was i.p injected with 2 mg/kg/bw of CdCl2, and the 4th group was injected with 2 mg/kg/bw of CdCl2 followed by oral administration with 50 mg/kg/b.w. PPE. Histopathological changes of liver were examined by light and transmission electron microscopes. Serum ALT and AST was determined and oxidative stress markers MDA, total antioxidant capacity (TAC) were measured in liver homogenate. The results showed that Cd induced several histological alterations in the liver including congestion of blood vessels, leucocytic infiltration, cytoplasmic vacuolation of the hepatocytes and fatty infiltrations. The ultrastructural changes include mitochondrial degeneration, swelling of rER and pyknosis of nuclei with increase in fat droplets and lysosomes. Biochemically, ALT and AST activities and MDA were increased levels while TAC was decreased. Treating mice with PEE with Cd improved the histological as well as ultrastructural structures. ALT, AST and MDA were reduced with increase in TAC. The results suggests that the ameliorative effect of PPE may be due to its antioxidant properties in combating free radical-induced oxidative stress and tissue injury resulting from cadmium chloride exposure. Key words: Cadmium, Pomegranate peels, Hepatotoxicity, Histology, Oxidative stress, Mice