Abstract: AIM: To study the effect of safflower yellow(SY) on the proliferation of vascular smooth muscle cell(VSMC) and the mechanisms.METHODS: The effect of SY on the proliferation of VSMC and the activities of three protein kinases (TPK,PKC,MAPK) in rabbit VSMC were studied by means of cell counting and 32P-incorporation.RESULTS: SY was shown to inhibit the proliferation of serum-induced VSMC in dose- and time-dependent manner. SY at the dose of 1.0 mg.mL^-1 significantly decreased the number of VSMC (the maxium inhibitory rate was 54.6%)； The effect of SY on VSMC showed maxium inhibition of 52.0% for 4 days；the inhibitory rate decreased over 4 days. SY decreased the incorporation of ³H-TdR in serum-stimulated VSMC， the maxium inhibition was 80.2% at the dose of 1.0 mg.mL^-1 for 2 days. As SY concentration increased， the activities of TPK,PKC and MAPK in serum-stimulated VSMC decreased， SY inhibited the activities of TPK,PKC and MAPK in VSMC and reach maxium at the dose of 1.0 mg.mL^-1 for 3 days(97.8%, 92.9% and 82.3% respectively). CONCLUSION: SY inhibited the proliferation of VSMC， the inhibitory effect of SY on VSMC proliferation might be due to inhibition of TPK, PKC and MAPK.