Abstract: Different parts of Croton zambesicus have been identified traditionally to possess various medicinal uses in Africa, such as for treatment of hypertension, dysentery, fever, convulsions, malaria and diabetes mellitus. The aim of this study was to examine the effects of methanol and aqueous extracts of C. zambesicus seeds at a dose of 75 mg kg-1/day and 300 mg kg-1/day in Wistar rats. The body, biochemical parameters and histopathological changes were assessed for the treated animals as well as those in the control group. The result of this study showed that, the extracts of C. zambesicus present significant beneficial effects on erythropoiesis and lowering cholesterol level which confirms the use of this plant in ethnomedical practice. But, these extracts at the doses administered were found to cause varies body weight changes and significant increase in ALT, AST and ALP activities as well as pathological changes such as fatty changes and necrosis in liver and kidney and the lymphocytic infiltration in intestinal lamina are all indicate that the plant extracts has the potential to cause toxicity and intestinal damage at dose dependant manner. But the exact chemical compound(s) responsible for these effects in the plant extracts still remains speculative.