In order to investigate the inhibitory effect of cariporide, a specific Na⁺/H⁺ exchanger 1 (NHE1) blocker, on neointimal proliferation induced by AGEs in a carotid artery balloon injury model, the rats carotid artery was balloon injured. The exemplars were collected and stained by HE. The morphology changes were observed. The intima area, media area and the ratio of area between intima and media were calculated using image analysis system. In order to explore the precise mechanism, the experiments were done on the isolated rat vascular smooth muscle cells(VSMC). Cell proliferation was assessed by [³H] thymidine incorporation. RT-PCR and Real-time RT-PCR were used to assay the cyclooxygenase-2 (COX-2) matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) expression; Western blot was used to assay NF-κB protein and the degradation of the inhibitor I-κBα. The in vivo results shows that neointima hyperplasia is significantly suppressed treated with cariporide in balloon-injured rats compared with AGEs treatment lonely. The in vitro study shows that cariporide dose-dependently inhibited AGEs-induced upregulation of COX-2, MMP-2 and MMP-9 expression. We also found that cariporide blocked AGEs-induced activation of nuclear factor-κB(NF-κB)and pointed out that inhibition of NF-κB was achieved by inhibiting the degradation of the inhibitor I-κBα. The results identified that NHE1 inhibitor cariporide inhibited AGEs-induced neointimal hyperplasia in rats balloon-injured model by suppressing the proliferation of VSMC and the upregulation of COX-2, MMP-2 and MMP-9 via inhibiting NF-κB activation in VSMC. These results indicated that NHE1 might be a considerable ingredient of the signal pathway in which AGEs played a key role in the processes of vascular damage.