Here, we investigated whether I(4), which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE(-/-) mice were fed a Western diet and simultaneously administered I(4), glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. mouse-monocyte-macrophage-leukemia-cells macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I(4). The data indicated that I(4) significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p?