Constriction and dilation of large arteries of brain regulates cerebral vascular resistance and cerebral microvascular pressure, which play key roles in regulation of cerebral circulation. We investigated the effect of ischemic stroke on vascular reactivity of middle cerebral artery (MCA) using a rat transient focal cerebral ischemia model. Focal cerebral ischemia was induced by 1 hour MCA occlusion followed by reperfusion. MCAs were dissected from ischemic or contralateral hemisphere at 2 days or 2 weeks post reperfusion and mounted on 2 glass micropipettes for assessment of vascular reactivity. MCAs from brains of sham surgeries were used as control. At 2 days post reperfusion, a significant alteration of myogenic reactivity was found in MCAs dissected from both ischemic and non-ischemic hemispheres, which could still be identified at 2 weeks after reperfusion. Phenylephrine (PE) induced remarkable vasoconstriction in MCAs from animals that underwent sham surgery. No significant alteration of vasoconstrictive response to PE was found in MCAs isolated from either ischemic or contralateral hemisphere at 2 days or 2 weeks after ischemic stroke, as compared with MCAs from sham animals. Acetylcholine (ACh) induced mild dilation in normal MCAs, which was reversed in MCAs from both ischemic and non-ischemic hemispheres at 2 weeks after ischemic stroke. Sodium nitroprusside (SNP) induced vasodilation in MCAs from animals with sham operation, which was diminished in MCAs from both ischemic and non-ischemic hemisphere at 2 days and 2 weeks after ischemic stroke. These results demonstrated that focal cerebral ischemia could induce long-term global cerebral vasculature dysfunction.