Stabilization of carotid artery plaques by pharmacologic intervention is a promising strategy for the prevention of ischemic stroke. In this study, we examined the effect of 12 months of statin therapy on carotid plaque echogenicity. This study included 81 hypercholesterolemic patients with carotid atherosclerotic plaques. Echogenicity of the largest plaque in each patient was evaluated by ultrasound with integrated backscatter analysis. All patients underwent dietary modification. Forty patients were treated with simvastatin (10 mg/day, n = 24) or atorvastatin (5 mg/day, n = 16) according to the choice by each attending physician. Carotid plaques were monitored by measuring plaque thickness and echogenicity during a 12-month follow-up period. Levels of serum high-sensitivity CRP (hs-CRP), interleukin (IL)-6 and IL-18 were determined in all patients. Total cholesterol, triglyceride, hs-CRP and IL-18 were significantly decreased after 12 months of statin therapy. The change in IL-6 level was not significant. Significant increases in echogenicity of carotid plaques and decreases in plaque thickness were noted after statin therapy. In the 41 patients without statin therapy, carotid plaque echogenicity, plaque thickness and serum levels of inflammatory markers were not significantly altered. Our results suggest that statin therapy in hypercholesterolemic patients for 12 months increases carotid plaque echogenicity and decreases plaque thickness, in addition to lowering serum levels of lipids and inflammatory markers.