In this study, the vascular responses of diabetic rat femoral arteries to epinephrine were investigated. The effects of lisinopril (ACE inhibitor) on vascular epinephrine sensitivity were also tested in a different group. This study was carried out in sodium pentobarbital-anesthetized rats 8 weeks after induction of diabetes with streptozotocin. After extensive dissection of the femoral arteries with adventitial stripping, epinephrine and chlorpromazine were applied to the vascular wall, and their vascular effects were compared in streptozotocin-diabetic (STZ-D), lisinopril-administered streptozotocin-diabetic (LASTZ-D), lisinopril-administered nondiabetic (LAND), and non-diabetic (ND) groups. Vasoconstriction was induced by epinephrine in all groups in a dose-response fashion. There were statistically significant differences in maximum percent constriction between STZ-D and LASTZ-D groups. There was also a significant increase in sensitivity to epinephrine in the STZ-D group. The vasoconstriction induced by epinephrine was relieved by chlorpromazine in all groups. Results suggest that there are important functional abnormalities in the responses of vessels to epinephrine in diabetics, and that the attenuation of vasoconstriction by ACE inhibitors may have beneficial effects in microsurgical procedures performed on diabetic patients. Topically-applied chlorpromazine appears to be effective in relieving vasospasm due to epinephrine, and may be a useful tool to resolve perioperative vascular spasm in microsurgical procedures for diabetic and non-diabetic patients.