The present study was aimed at evaluating the effect of methanol leaf extract of Croton zambesicus on hemoglobin (Hb), serum aspartate aminotransferase (AST), alanine aminotransferase ALT) and liver histology of albino mice. Mice of both sexes (n=24), weighing between 20-25g were distributed into four groups, I-IV. Group I orally received 5 ml/kg normal saline and served as the control. Groups II-IV received the extract orally at respective doses of 500 mg/kg, 700 mg/kg and 900 mg/kg. Treatments lasted for five days, and on the sixth day blood samples were taken from the sacrificed animals in order to evaluate the levels of the parameters. Carefully excised liver samples were fixed in 4% formaldehyde for detailed examination. The parameters were assessed for the treated animals as well as those in the control group. The Hemoglobin value was observed to increase from 90.83 g/L (for the 500 mg/kg extract group) to 95.17 g/L (900 mg/kg extract group). The AST values decreased from 28.50 iu/L (500 mg/kg extract group) to 22.00 i.u/L (900 mg/kg extract group).The ALT values were also observed to decrease from 25.00 i.u/L(at 500 mg/kg extract dose) to 22.0 i.u/L(at 900 mg/kg extract dose). The differences in the values were not significant (p>0.05) as compared with the controls. Histological examinations showed that all liver samples showed well preserved hepatocytes. It was thus concluded that the extract did not elicit any deleterious effect on the hepatic tissues/hematology of the animals.