We evaluated the protective potential of anthocyanins from purple sweet potato Ipomoea batatas cultivar Ayamurasaki (APSP) against low-density lipoprotein (LDL) oxidation in vitro and atherosclerotic lesion development in apolipoprotein E-deficient mice given a cholesterol- and fat-enriched diet with or without 1% APSP for 4 weeks. APSP protected LDL against oxidation more potently than other anthocyanins and l-ascorbic acid in vitro. In mice, APSP significantly lowered the atherosclerotic plaque area to about half of the control, the liver level of thiobarbituric acid-reactive substances as an oxidative stress marker, and the plasma level of soluble vascular cell adhesion molecule-1 (sVCAM-1). However, APSP showed no effects on body weight and cholesterol and lipid levels in the plasma. The results suggest that APSP can suppress the development of atherosclerotic lesions and both enhancements of oxidative stress and sVCAM-1 independently of the changes in cholesterol and lipid levels in mice.