Lead is one of the most toxic metals, producing severe organda mage in animals and humans. Oxidative stress reported to play an important role in lead acetate induced liver injury. This study was carried to investigate the role of ethanol extract of mangos teen pericarp in protecting against lead acetate-induced hepatoxicity in male mice.The sample used 50 male mice were divided into 5 groups: negative control (mice were given daily with aquadest); positive control (mice were given daily with lead acetate 20 mg/kg BW orally once in a day for 21 days); and the treatment group ( mice were given the mangos teen pericarp extracts200 mg; 400 mg; 800 mg/kg BW orally once in a day for 25 days, and on 4th day, were given lead acetate 20 mg/kg BW one hour after the mangos teen pericarpextracts administration for 21 days). On day 25 measured levels of Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvate Transaminase (SGPT), Alkaline Phosphatase (ALP), Malondialdehyde (MDA), Superoxide Dismutase (SOD)and Glutathione Peroxidase (GPx). The SGOT, SGPT, ALP, MDA, SOD and GPx data were analyzed with one-way ANOVA, followed by LSD test. The results showed that, Oral administration of lead acetate 20 mg/kg BW for 21 days resulted in a significant increase in SGOT; SGPT, ALP and MDA level. Moreover, significant decrease in SOD and GPx. Treatment with the mangos teen pericarpextracts800 mg/kg BW but not 200 mg/kg BW and 400 mg/kg BW significantly (P< 0.05) decreased the elevated SGPT; SGOT, ALP and MDA levels as compared to positive control group. Treatment with the mangosteen pericarpextracts 800 mg/kg BW also significant increase in SOD and GPx as compared to positive control group. From the results of this study concluded that the mangos teen pericarpextractscould be a potent natural herbal product provide a promising hepato protective effect against lead acetate induced hepato toxicity in mice