The protective effect of nilvadipine, a Ca²⁺ antagonist, on cerebral ischemia was investigated in spontaneously hypertensive rats. The 12-week-old animals were treated for 7 days with either nilvadipine or vehicle using osmotic pumps implanted subcutaneously. Group 1 animals (n = 10) received the vehicle, and Group 2 (n = 10) and 3 animals (n = 10) received 1 and 3 mg/kg/day nilvadipine, respectively. The left middle cerebral artery was occluded under halothane anesthesia on the 6th day of treatment, and neuropathological outcomes were quantified 24 hours later. The systolic blood pressure measured before occlusion decreased to 137 ± 9 mmHg (Group 2) and 130 ± 9 mmHg (Group 3), compared to 189 ± 12 mmHg for Group 1 (p < 0.05). The percentage infarct volumes in Groups 1-3 were 39 ± 3%, 37 ± 2%, and 34 ± 3%, respectively (p < 0.05, Groups 1 vs. 3). Therefore, nilvadipine decreased the infarct size dose-dependently. Nilvadipine has a protective effect against cerebral ischemia in rats with chronic hypertension. Neuropathological findings suggest that nilvadipine may act at the ischemic penumbra. Nilvadipine may have the additional benefit of reducing the consequences of a possible later stroke in patients with hypertension (one of the risk factors for stroke).