Aim To investigate the effect of capsaicin on the inhibition of rat vascular smooth muscle cells (VSMC) induced by high sodium. Methods Vascular smooth muscle cells were isolated from thoracic aorta of male Sprague-Dawley rats by tissue adherent method, and the growth curve of vascular smooth muscle cells was made according to MTT assay. The experimental procedures were performed with the fourth generation of vascular smooth muscle cells. Vascular smooth muscle cells were synchronized by serum starvation for 24 h before capsaicin and high sodium treatment. Vascular smooth muscle cells were treated with different concentration of capsaicin (0.1,0.1,1, 10 and 100 μmol/L) for 72 h in high sodium. The effects of different concentration capsaicin and osmotic pressure on the proliferation induced by high sodium medium in vascular smooth muscle cells were evaluated by MTT assay and CCK-8, respectively. The cell cycle of vascular smooth muscle cells was analyzed by flow cytometry technology. The localization and protein expression of PCNA were employed by immunofluorecence staining and Western blot. The mRNA and protein expressions of TRPV1 were detemined by real-time PCR and Western blot. Results MTT results showed that when the concentration of capsaicin was 10 μmol/L, the proliferation of rat vascular smooth muscle cells began to be inhibited, and the inhibitory effect was increased at 100 μmol/L (P＜0.05), so 10 μmol/L capsaicin was selected for subsequent experiments. CCK-8 results showed that the cells in high sodium group proliferated obviously, but there was no difference between mannitol group, normal group and capsaicin group. Capsaicin prevented notably the decrease of cell number in G0/G1 and G2/M stage and increase of cell number of S stage in vascular smooth muscle cells treated with Na＋ (159 mmol/L). PCNA protein level was also decreased by capsaicin. The decrease of mRNA and protein level of TRPV1 stimulated Na＋ (159 mmol/L) was alleviated by capsaicin. Conclusion Capsaicin can inhibit the proliferation of vascular smooth muscle cells induced by Na＋ (159 mmol/L), the mechanism may be related to the up-regulation of TRPV1 expression.