In this study, antioxidant activity of methanol extract of stem bark of Spondias mombin (MESPM) was investigated using carbon tetrachloride (CCl4)-intoxicated rat liver as the experimental model. The intoxicated rats were administered MESPM for 14 days (daily, orally at the dose of 200 mg/kg and 400 mg/kg body weight) and silymarin at the dose of 50 mg/kg body weight. In vivo antioxidant activities of SPMME have been evaluated by using a range of methods such as measurement of lipid peroxidation by thiobarbituric acid reactive substances (TBARS), 2, 2’- diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant of plasma (FRAP) assay. Oral administration of MESPM and reference drug silymarin in intoxicated rats reduced significantly TBARS level in both serum and liver tissues and also increased significantly FRAP values and percentage inhibition of DPPH radical compared to CCl4 group. At the dose of 400 mg/kg body weight, MESPM restored significantly of these values towards normal as a reference drug silymarin compared to control group in all assays. S. mombin possesses in vivo antioxidant activity and can be employed in protecting tissue from oxidative stress.