BACKGROUND AND OBJECTIVES: The present study investigated differences in the effects of macrophages between neointimal formation after balloon (BI) and that after stent injury (SI) in hypercholesterolemic rabbits. We also studied the relationship between advanced glycation end products (AGE), the receptor for AGE (RAGE), and S100A8/A9 in the inflammatory reaction mediated by macrophages. MATERIALS AND METHODS: Male New Zealand White rabbits fed with a 1% cholesterol diet for 2 weeks underwent balloon dilatation to one iliac artery, and stenting to the contralateral artery. Arteries were harvested at 7, 14, and 28 days after injury. RESULTS: Sizes and cell numbers of neointima were higher in SI than in BI (p<0.05), but those from media showed no difference between SI and BI (p>0.05). Sizes and cell numbers of neointima in BI and SI increased significantly till 14 days (p<0.05). Macrophage numbers increased in neointima of BI at 14 days (p=0.011), but not at 28 days (p>0.05). Macrophage numbers increased until 28 days in the media of BI (p=0.003). Macrophage numbers increased at 14 days in the neointima of SI (p=0.001), but decreased at 28 days (p=0.014). Macrophage numbers were not changed in the media of SI. Cell numbers and area were significantly correlated with macrophage numbers in the neointima and media of BI, and in the neointima of SI (p<0.05). RAGE expression was strong in cells adjacent to lumen at 7 and 14 days, and in cells of neointima and media adjacent to internal elastic lamina at 28 days. Expression of RAGE was increased in both macrophage and smooth muscle cells. Macrophages were the predominant cells observed with AGE accumulation. S100A8/A9 was not found. CONCLUSION: There seems to be a difference in effect of macrophages on the formation of neointima after injury between BI and SI. The effects of macrophages appears to be more significant in the neointima of BI. Mechanical arterial injury induces the formation of AGE and overexpression of RAGE in macrophages.