Background: Diabetes mellitus (DM) is one of the most common endocrinal diseases characterized by hyperglycemia and altered metabolism of lipids, carbohydrates, and proteins with an increased risk of many complications. Bioactive drugs extracted from natural sources had been used in a wide range of treatment for many diseases. This work aimed to investigate the potential antidiabetic effect of Egyptian honey bee venom (BV) in alloxan-induced diabetic rats. Subjects and methods: Forty adult male albino rats (140-180 g) were used in the study and divided into five groups each of eight rats. The normal control group, diabetic group, high-and low-dose BV-treated groups, and vildagliptintreated group. Blood samples and pancreases were collected after 6 weeks of the experiment. Results: Treatment of diabetic rats with BV revealed a significant decrease in serum glucose level accompanied by a significant increase in insulin level. Malondialdehyde (MDA), cholesterol, triglycerides, creatinine, and aminotransferases (ALT and AST) levels were significantly decreased after BV treatment in comparison with diabetic animals. Total antioxidant capacity (TAC), glutathione (GSH) contents, and catalase (CAT) activity had improved. Histological examination of the pancreas indicated a marked improvement in the islet architecture and marked regeneration of insulin-secreting β-cell in diabetic BV-treated rats. Conclusion: The study concluded that BV could have the ability to lower glucose level in diabetic rats and enhance insulin secretion, and relieved the various biochemical and histological abnormalities resulted due to diabetes metabolic disorders.