Aim To explore whether Na + H + exchanger (NHE) modulated atherogenesis, we investigated the effects of cariporide, a selective inhibitor of Na +- H + exchanger, against atherogenesis in animal models induced by high fat plus high cholesterol (high lipid) diet. Methods 22 healthy New Zealand rabbits were randomly divided into 3 groups: one group was fed normal chow (n=6), another group was fed high lipid diet chow served as atherogenesis control (n=8), the third group fed high lipid diet chow plus orally cariporide (0.1 mg/kg everyday) served as drug treated group (n=8). The blood was drawn from the central ear artery to assay serum lipoprotein at the prior experiment and animal sacrifice. Animals were killed in tenth week; the samples of arteries, lives and hearts were taken for morphologic analysis. Results The ultrastructures of aortic arteries showas follows. In normal diet group, the vascular intima were smooth and intact. In high lipid diet model group, the intima were become rough and thicker. A lot of lipoid foam cells migrated to regions of intima and smooth muscle cells (SMC) which associated injuries of internal elastic lamina. In the cariporide treated group, above described vascular injuries were significantly ameliorated, but it also was found that a few of foam cells scattered under intima of artery in a few cases (one rabbit). TC and low density lipoprotein cholesterol (LDLC) was significantly increased in both groups. Cariporide did not black increases of serum TC and LDLC levels. Conclusion Cariporide significantly decreased atherogenesis induced by hyperlipidemia. The actions of cariporide against atherogenesis were independent decreasing lipemia and mainly located in blood vessels and tissue.