Abstract: OBJECTIVE To evaluate the hepatotoxicity of pomegranate fruit peel ethanol extract in mice. METHODS An experimental study was carried out in mice. After random allocation of the intervention, forty mice were received pomegranate fruit peel ethanol extract(30, 45, 60 mg·kg^-1) or distilled water while in a fasted state for 12 h. After 24 h, the level of serum enzyme was measured with automatic biochemistry analyzer, which included ALT, AST, and LDH. MDA, GSH and GSSG were measured in liver homogenates to assess the oxidative damage. Histological changes in liver were observed by HE staining. RESULTS Compared with the control group, there were significant decreases of body weight, liver weight, liver weight and body weight ratio, significant increases of ALT, LDH, MDA, GSH/GSSG in both the middle and high dose of pomegranate fruit peel ethanol extract groups(P<0.05), and significant increase of AST in the high dose group. CONCLUSION These results indicates that oral administration of pomegranate fruit peel ethanol extract afford statistically significant toxicity to mice liver, and thus, the higher the dose, the more serious liver damage.