The liver as a major organ of metabolism is one of the first predisposed organs to food chemicals. Icacinia manni tuber, the examined agent in this study has claims of direct and indirect consumption by man as it is observed to be a source of energy which contains high amount of carbohydrates among other nutritional and anti-nutritional constituents. Four (4) weeks old Male Wistar rats were used for this study. They were fed with rat chow from vital feeds and allowed free access to drinking water throughout the experimental period. Icacinia manni tuber was washed with water to remove sand, cut into pieces and sun dried. The dried specimen was extracted with 80% Ethanol. After two (2) weeks of drying, the tuber was reduced into powder. The powder was divided into two parts. One part was macerated in 80% ethanol for 72hrs to give the crude ethanolic extract. The other part was successively macerated for 72hrs in n-hexane and ethanol to give the corresponding gradient fraction of these solvents. The liquid filtrate was concentrated and evaporated to dryness using rotary evaporator. The median lethal dose (LD50) of the extract was estimated using albino Wistar mice by intra peritoneal (ip) route. The rats which weighed between 60 and 100gm were randomly assigned four (4) groups. Group A served as the control and was given distilled water by mouth and allowed liberal food and water throughout the experimental period which was 28 days. Group B, C and D had low, intermediate and high dose of extract. Group B received 1/10 of LD50 by feeding tube i.e. 1/10 x 894.43 mg/kg = 89.44mg/kg. Group C received 2/10 of LD50 by mouth through a feeding tube i.e. 178.88mg/kg. Group D received 3/10 of LD50 by mouth through a feeding tube i.e. 268.32mg/kg. Stock concentration was 50mg/ml. On the twenty-eighth (28th) day, the animals were anaesthetized with chloroform. Blood samples were obtained by cardiac puncture. Serum obtained for biochemical analysis. The livers were harvested for histological analysis. The results showed significant higher levels (p˂0.01) of Mean Total Cholesterol and High Density Lipoprotein in treated rats compared to the untreated rats. Significant lower levels (p˂0.01) of Mean Triglycerides and Low Density Lipoprotein were observed in untreated rats compared to treated rats. The Mean Total Protein, Mean Albumin and Mean Globulin levels for treated rats were significantly lower (p˂0.01) than that of the untreated rats. The histologic photomicrographs of liver of treated rats showed moderate area cellular abnormalities with area of vascular congestion and degeneration, cellular degeneration, vacuolization and pyknotic nuclei as compared to untreated rats. This study shows the hepatotoxicity of Icacinia manni tuber and its associated risk of metabolic syndrome.