Aims: Previous studies suggest that both statins and calcium-channel blockers inhibit cardiovascular and cerebrovascular diseases by their pleiotropic effects, such as antioxidation and anti-inflammatory actions. By using stroke-prone spontaneously hypertensive rats (SHRSPs), the isolated effect of each pharmaceutical has been reported, but the effect of a combination of both pharmaceuticals has not been reported. In this study, we evaluated combination therapy of atorvastatin and amlodipine for its efficacy in preventing stroke in the SHRSP model. Main Methods: We initiated treatment of SHRSPs at 8 weeks of age with atorvastatin (2 mg/kg), amlodipine (1 mg/kg), a combination of atorvastatin (2 mg/kg) and amlodipine (1 mg/kg), or vehicle. Measurement of physiological parameters and immunohistochemical assessments for oxidative stress and inflammation were done at each group. Key findings: At 13 weeks of age, the combination therapy group showed greater inhibition of an antioxidation and anti-inflammatory marker than the vehicle group, although there were no differences in blood pressure. Significance: Our study suggests that the combination therapy of atorvastatin and amlodipine may protect against hypertension-induced stroke by the additive effect of the antioxidation and the anti-inflammatory action of the both agents.