Aim To evaluate the effect of advanced glycation end products(AGE) on the activity of Na+/H+ exchanger 1(NHE1) of vascular smooth muscle cell(VSMC) in rats. Methods Patch-attaching method was used in primary and continuous culture of the VSMC.The cultured VSMC of rat were exposed to AGE for 24 hours,and the activity of NHE1 was observed by using the fluorescent dye BCECF. Results AGE at concentration 1,5,10 mg/L can concentration-dependently increase the NHE1 activity,from 0.66±0.05 to 0.71±0.03,0.80±0.07,0.88±0.06 respectively;Results of RT-PCR showed that AGE can significantly increase the expression of NHE1 mRNA from 0.77±0.07 to 0.88±0.08,1.23±0.06,1.33±0.08 respectively(P<0.05 or P<0.01);Pretreatment with the inhibitor of the receptor for advanced glycation end products(RAGE) anti-RAGE and inhibitor of mitogen-activated protein kinase(MAPK)PD98059 at concentration 1,10,25 μmol/L can significantly decrease the NHE1 activity from 0.94±0.05 to 0.86±0.06,0.74±0.05,0.66±0.07 respectively compared with the AGE treatment group(P<0.05 or P<0.01). Conclusion AGE can significantly increase the NHE1 activity,and the mechanism may be related to the RAGE activated and the MAPK.