Our goals were to determine whether the response of the rat isolated basilar artery to activation of ATP-sensitive potassium (K ATP ) channels is altered in diabetes mellitus, and to determine the effect of chronic insulin treatment on this response in established diabetic rats. The relaxation induced by cromakalim, an activator of K ATP channels, was significantly weaker in insulin-untreated streptozotocin-induced diabetic rats than in the controls. This impairment was significantly improved following chronic administration of insulin. The relaxations induced by two Ca 2+ -activated K + -channel activators [1-ethyl-2-benzimidazolinone (1-EBIO) or 1, 3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS1619)] were not significantly different between control and insulin-untreated diabetic rats. The sodium nitroprusside-induced relaxation was similar among the three groups (control, diabetic, and insulin-treated diabetic). These results suggest that: (a) the impaired cromakalim-induced relaxation seen in diabetic rats is not due to a nonspecific effect of diabetes mellitus on vasorelaxation, but at least partly to an effect on K ATP channels, and (b) that this impaired relaxation can be restored by chronic insulin treatment.