This study was designed to evaluate the hepatoprotective effect of Alpha-melanocyte Stimulating Hormone (α-MSH) against Carbon tetrachloride (CCl₄) induced hepatotoxicity in experimental rats in vivo. Sixty male Wister rats weighing 160-190 g respectively were used for the study and were divided into four groups, with 15 animals in each group. Group I consisted of nonhepatotoxic rats that received only the vehicle (0.5 mL/kg body weight) and served as a control group. Group II, the animals were injected intramuscularly with hormone α-MSH (sigma formula) 2mg/100g of body mass every alternate day for 15 days. Group III administered carbon tetrachloride (CCl4; 2 ml/kg body weight) rally every alternate day for 15 days to produce the hepatotoxity in rats. Groups IV (treated hepatotoxic group), the animals were administered CCl4; 2 ml/kg body weight and treated with hormone α-MSH (sigma formula) 2mg/100g of body mass every alternate day for 15 days. At the end of the experiment, the animals were sacrificed and blood was collected directly. Serum was separated after and analyzed for various biochemical parameters, i.e. Alanine transaminase (ALT), Aspartate transaminase (AST), alkaline phosphates (ALP), total and direct bilirubin, total protein and albumin. Our results showed that the administration of 2 ml/kg body weight of carbon tetrachloride (CCl₄) every alternate day for 15 days has enhanced the ALT, AST, ALP, total and direct bilirubin and liver weight, and reduced the total protein and albumin in comparison with the control group. The treatment with hormone α-MSH (sigma formula) 2mg/100g of body mass has brought back the altered levels of biochemical markers to the near normal levels. In our study, we observed that there is a significant (P < 0.05) increase in the concentration of total cholesterol, triglycerides, LDL cholesterol and a significant (P < 0.05) decrease in HDL cholesterol in the hepatotoxic rats. Also we investigated some hematological parameters and It was found that the RBC and WBC count, PCV, Hb, ESR, neutrophil percentage and lymphocyte percentage were significant decreased (P <0.05) in the hepatotoxic rats and the treatment with alpha melanocyte stimulating hormone (alpha-MSH) cased significant increasing in these hematological parameters. It was concluded from the result that the hormone α-MSH possesses hepatoprotective activity against carbon tetrachloride (CCl₄) induced hepatotoxicity in experimental rats.