This study was aimed at evaluating the histological and biochemical effects of ethanol leave extract of Azadirachta indica and melatonin in streptozotocin-induced diabetic Wistar rats. To achieve this, forty five Wistar rats were used in the study. The animals were assigned into the following groups: Group 1: Normal control + normal saline orally; Groups 2: Normal + A. Indica (200mg/kg b w) orally; Group 3: Normal + melatonin (10 mg/kg b w) IP; Group 4: Normal + melatonin (10 mg/kg b w) IP + A. Indica (200 mg/kg b w) orally; Group 5: Diabetic control + normal saline orally; Group 6: Diabetic + A. Indica (200 mg/kg b w) orally; Group 7: Diabetic + melatonin (10 mg/kg b w) IP; Group 8: Diabetic + A. Indica (200 mg/kg b w) orally + melatonin (10 mg/kg b w) IP; Group 9: Diabetic + metformin (500 mg/kg b w) orally. The extract and drug were administered once daily for a period of three (3) weeks respectively. After the last day of treatment, the animals were sacrificed and the liver tissues were collected and processed histologically and specially stained with PAS for glycogen, Gordon and Sweet for reticular fibers and HVG for collagen fibers. The serum liver enzyme activities were also determined. The results showed regeneration of liver collagen and reticular fibers and improved hepatic glycogen stores in all extract and melatonin treated diabetic groups and as well as the extract and melatonin when combined as compared to diabetic control group. On the other hand there was a significantly (p<0.05) reduced levels of liver enzyme activities in the extract and melatonin treated diabetic groups as well as in the extract and melatonin when combined as compared to diabetic control group.