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Abstract: Endomorphins, the endogenous, potent and selective μ-opioid receptor agonists, have been shown to decrease systemic arterial pressure (SAP) in rats. In the present study, responses to endomorphins were investigated in systemic vascular bed of alloxan-induced diabetic rats and in non-diabetic rats. Diabetes was induced by alloxan (220mg/kg, i.p.) in male Wistar rats. At 4–5 weeks after the onset of diabetes, intravenous injections of endomorphins (1–30nmol/kg) led to an increase of SAP and heart rate (HR) consistently and dosed-dependently. SAP increased 7.68±3.73, 11.19±4.55, 21.19±2.94 and 27.48±6.21% from the baseline at the 1, 3, 10 and 30nmol/kg dose, respectively, of endomorphin 1 (n =4; p <0.05), and similar changes were observed in response to endomorphin 2. The hypertension could be antagonized markedly by i.p. 2mg/kg of naloxone. On the other hand, bilateral vagotomy would attenuate the effects of hypertension and diminished the changes of HR in response to endomorphins. With diabetic rats, 6–10 weeks after the induction of diabetes, intravenous injections of endomorphins produced non-dose-related various changes in SAP, such as a single decrease, or a single increase, or biphasic changes characterized by an initial decrease followed by a secondary increase, or no change at all. These results suggest that diabetes may lead to the dysfunction of the cardiovascular system in response to endomorphins. Furthermore, the diabetic rats of 4–5 weeks after alloxan-treatment, the increase in SAP and HR caused by i.v. endomorphins might be explained by a changed effect of vagus and by a naloxone-sensitive mechanism. [Copyright &y& Elsevier]