Background Recent evidence suggests that oxidative stress may play a role in the development of atherosclerosis. MCI-186 (3-methyl-1-phenyl-1-parazolin-5-one, edaravone) is a novel free radical scavenger, but it remains unclear whether free radical scavengers would be effective for the prevention of the disease. Methods and Results Experimental atherosclerosis was induced in apolipoprotein E-deficient mice fed a high-fat diet containing 0.3% cholesterol. Mice were treated with an intraperitoneal injection of either MCI-186 1 mg/kg per day or MCI-186 10 mg/kg per day on alternate days over 4 weeks. Fatty streak lesion was suppressed by MCI-186 10 mg/kg per day administration, but not by mg/kg per day. Immunohistochemical analysis showed that macrophage and CD4⁺ T-cell accumulation and oxidative stress overload in the fatty streak lesion were suppressed in mice that received MCI-186 treatment. Conclusions MCI-186 administration suppressed the development of atherosclerosis, associated with reduced expression of both immune-activated cells and oxidative stress in fatty streak plaques. (Circ J 2006; 70: 1216 - 1219)