ObjectiveTo evaluated the differential effects of ethanol extraction of Citrullus colocynthis (C. colocynthis) on the blood glucose concentration and pathology of pancreas, liver, lungs, kidney and gastrointestinal tract in the alloxan induced diabetes in rats. MethodsDiabetes mellitus was induced in 20 adult female Albino rats, using intraperitoneal injection of 120 mg/kg alloxan. The diabetic rats were randomly assigned into two equal groups. The first group was treated with the extract of C. colocynthis seed (300 mg/kg) and the rats of the second group, as an untreated diabetic group, received ordinary diet. Ten non diabetic rats remained as a normal control group. ResultsThe results of this study indicate that C. colocynthis was able to reduce blood glucose significantly compared with the control diabetic group (P<0.05). Histopathologically, alloxan resulted in severe necrotic changes in the pancreatic islets, especially in the central area of the islets. Tissue sections of the pancreas in the treated rats demonstrated enhanced regeneration of B cells and increased size of pancreatic islets. Liver of the treated diabetic rats revealed significant improvement of the hepatic tissue compared to those of the untreated diabetic rats. ConclusionsThe present study indicated a significant anti-hyperglycemic effect of C. colocynthis seed and supported its traditional usage in treatment of diabetes mellitus.