Experimental studies have demonstrated that oxidative stress and apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The purpose of this study was to determine whether the quercetin dihydrate (Q) protects against cerebral ischemia neuronal damage. Male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h and reperfused for 72 h. Quercetin (30 mg/kg, i.p) was administrated 30 min before the onset of ischemia and after the ischemia at interval of 0, 24, 48, and 72 h. The administration of Q showed marked reduction in infarct size, reduced the neurological deficits in terms of behaviors, suppressed neuronal loss and diminished the p53 expression in MCAO rats. Q was found to be successful in upregulating the antioxidant status and lowering the TBARS level. Conversely, the elevated activity of poly (ADP-ribose) polymerase (PARP), and activity of caspase-3 in MCAO group was attenuated significantly in Q treated group when compared with MCAO group. Our study reveals that Q, as a powerful antioxidant, could prevent free radicals associated oxidative damage and morphological changes in the MCAO rats. Thus, it may have a therapeutic value for the treatment of stroke.