<p><b>OBJECTIVE</b>To study the action mechanism of tetramethylpyrazine (TMP) on the proliferation of vascular smooth musclecells (VSMCs), thus providing experimental evidence for Chinesemedicine to effectively prevent restenosis.</p><p><b>METHODS</b>Rats' thoracic aorta VSMCs in vitro cultured (cell line A7r5) were divided into five groups, i.e., the negative control group, the angiotensin II (Ang II, 10(-6) mol/L) group, the low doseTMP (20 micromol/L) plus Ang II group, the middle doseTMP (40 micromol/L) plus Ang II group, the high doseTMP (80 micromol/L) plus Ang II group. The proliferation ratio was detected by MTT. Gene and protein expressions of Wnt4, Dvl-1, beta-catenin, CyclinD1, and collagen I and III were detected with real-time fluorescent quantitative PCR and Western blot respectively.</p><p><b>RESULTS</b>Compared with the negative control group, the proliferation ratio of VSMCs obviously increased in the Ang II group (P < 0.05). Compared with the Ang II group, the proliferation ratio of VSMCs obviously decreased in the middle doseTMP plus Ang II group and the high doseTMP plus Ang II group (P < 0.05). Compared with the negative control group, gene and protein expressions of Wnt4, Dvl-1, beta-catenin, CyclinD1, Col I, and Col III were obviously up-regulated in the Ang II group (P < 0.05). Compared with the Ang II group, mRNA and protein expressions of Wnt4, Dvl-1, beta-catenin, CyclinD1, Col I, and Col III were obviously down-regulated in the middle doseTMP plus Ang II group and the high doseTMP plus Ang II group (P < 0.05). The aforesaid indices were dose-dependent in the low, middle, and high doseTMP plus Ang II groups.</p><p><b>CONCLUSION</b>TMP inhibited Ang II induced proliferation and collagensecretion of VSMCs through down-regulating Wnt signal pathway.</p>