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Previous studies showed that sodium ferulate, the effective component of Chinese herb, can inhibit platelet aggregation and decrease serum lipid. However, it is still unknown if sodium ferulate could prevent atherosclerogenesis. The experiments were designed to study its effects and mechanisms on atherosclerogenesis. Blood samples and thoracic aortas obtained from Japanese rabbits fed by high-lipid or high-lipid plus sodium ferulate forage were analyzed and compared. Simultaneously, vascular endothelial cells were cultured and treated by hyperlipidemic serum solely or plus sodium ferulate. Cellular ultrastructure, nitric oxide (NO) production, and cytokines expressions were studied and compared. In vivo experiment, aorta atherosclerotic plaque area of sodium ferulate-treated rabbits was much smaller than that of high-lipid–fed rabbits and serum triglyceride was correlated positively with the plaque area in both groups. In vitro, endothelial cells incubated with hyperlipidemic serum exhibited pronounced ultrastructural abnormalities, transforming growth factor β1 expression and NO release were significantly decreased, while basic fibroblast growth factor expression was increased. Interestingly, the treatment group results clearly demonstrated that sodium ferulate was effective to protect cells from detrimental effects of hyperlipidemic serum and to help maintain normal NO and cytokines expressions. We concluded that sodium ferulate could inhibit rabbit aorta atherosclerogenesis, possibly through decreasing the serum lipid concentration and preventing vascular endothelial cells from the injury of hyperlipidemic serum.