Introduction: Syzygium cumini (SC) L skeels seeds were traditionally used as anti-diabetic plant in India. Protease inhibitors are the small defensive proteins present in the seeds that interfere with the growth and development of phytophagous insects. Objective: To partially purify the protease inhibitors from the seeds of SC and to evaluate the sub chronic toxicity and anti-diabetic activities of the SC derived protease inhibitors Methods: Acute and sub chronic toxicity studies were evaluated for the protease inhibitor purified from the SC seeds. Various physiological, biochemical parameters were evaluated for the treated rats. Anti diabetic activity of the above purified protease inhibitor was evaluated by checking the food intake, water intake, body weight, SGPT, SGOT, ALP, creatinine, blood glucose, insulin, oral glucose tolerance studies and histopathology study of pancreatic slides. Results: We observed no lethality upto dose of 2000 mg/kg body weight. After fifteen days of oral administration we observed no significant difference was observed in the rats treated with SCPI (200mg/kg) for 15 days on the body weight, food intake, and water consumption. Various biochemical, hematological and histopathological studies had shown no significant difference compared to the normal animals. Diabetes was induced by streptozotocin and various serum parameters were investigated. We observed a significant decrease in the physiological, biochemical and histopathological parameters in the protease inhibitors treated groups in dose dependent. Conclusion: The above result confirms that protease inhibitor derived from the SC has no toxicity in acute and sub chronic toxicity, can be effectively used as anti-diabetic herbal drug
