The effects of 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA) originating from Korean cabbage kimchi were investigated, showing an antioxidant effect on the prevention of atherosclerosis in hypercholesterolemic rabbits. Twenty-one 3-month-old rabbits were fed an atherogenic diet containing 0.5% (w/w) cholesterol and 10% (w/w) coconut oil, whereas another two groups were given an atherogenic diet with intravenous injection of either HDMPPA or simvastatin (0.33 mg/kg/day) for 4 weeks. HDMPPA inhibited the oxidative modification of low-density lipoprotein (IC 50 = 1.4 microg/mL) and increased 2,2'-diphenyl-1-picrylhydrazyl radical scavenging activity (IC 50 = 0.78 microg/mL) in a dose-dependent manner. In hypercholesterolemic rabbits, the thickness of intima of aorta of the HDMPPA group was significantly reduced (control versus HDMPPA, 42%; simvastatin, 38%) without a plasma cholesterol-lowering effect. Thiobarbituric acid reactive substance formation in the plasma of the HDMPPA group was significantly decreased compared to that of the control group. Furthermore, the generation of vascular reactive oxygen species in HDMPPA group was suppressed as the cyclooxygenase-2 protein level decreased. These findings suggest that HDMPPA prevents the development of aortic atherosclerosis in high-cholesterol-fed rabbits. The antiatherosclerotic effect of HDMPPA may be due to an antioxidative effect at a low dose without cholesterol-lowering effects.