Antimalarial drug toxicity is viewed different, depending on if the clinical indication is for treatment or prophylaxis. In drug therapy of Plasmodium falciparum malaria, which has a high mortality if untreated, a greater risk of adverse reactions to antimalarial medication is inevitable. The effect of the administration of Artesunate on the liver of wistar rats was studied. Study design was experimental and deployed clinical laboratory assessments. Four groups of wistar rats, each of five animals weighing between 100-150 g were used. Group 1 served as the control and was administered normal feed and drinking water. Group 2, 3 and 4 received 0.24mg/kg, 0.34mg/kg and 76mg/kg body weight Artesunate daily respectively, orally for four weeks. Serum Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) activities and Bilirubin were determined at the end of the treatment. Results showed that in group 3 and 4, there was a significant increase in serum AST and ALT and a significant decrease in serum ALP. The results also showed that at mild doses (0.24mg/kg and 0.34mg/kg), Artesunate promoted weight gain and at highest dose (76mg/kg), it appeared to result in reduced percentage weight gain suggesting perhaps that high doses were toxic. It is concluded, that administration of high doses of Artesunate by the oral route produced considerable damage to the liver.