Leptin and endothelin (ET), as important endogenous factors, interact with each other which may contribute to a better understanding of their role in diabetic pathogenesis. We aimed to evaluate the relationship between leptin and ET by investigating the influence of BQ-123, an ET-A receptor (ETAR) antagonist, on leptin levels in rats with diabetes induced by streptozotocin (STZ). In this study, 24 male, Wistar-albino rats were divided into three groups: Control, STZ, STZ + BQ-123 groups. BQ-123 relatively reduced oxidative stress and leptin levels. ETAR antagonist BQ-123 has positive impacts, depending on the dosage in the diabetic rats.