Objective: To investigate the effects of soy isoflavone on the proliferation of cultured rat vascular smooth muscle cell (VSMC) induced by angiotensin Ⅱ. Methods:VSMCs were primary cultured by tissue sticking method. Cell proliferation model was established by stimulation with AngⅡ. Cell proliferation was measured by MTT assay and CellTiter-Glo■ assay to observe the effects of various concentrations of soy isoflavone and NG-nitro-L-arginine methyl ester(L-NAME, 100 μmol/L) on VSMC proliferation induced by AngⅡ. Nitric oxide (NO) level was measured by Griess reagent. Nitric oxide synthase (NOS) and inducible nitric oxide synthase (iNOS) levels were detected by chemical colorimetric method. mRNA expression of iNOS was measured by reverse transcription polymerase chain reaction (RT-PCR). Results: Soy isoflavone ranging from 0.1~1.0 μmol/L inhibited cell proliferation in a dose-dependent manner. The inhibitory effects were partly blocked by 100 μmol/L of L-NAME. Soy isoflavone markedly increased NO, NOS and iNOS levels, and increased iNOS mRNA expression in VSMC. Conclusion: Soy isoflavone could inhibit VSMCs proliferation induced by AngⅡ. The increase of NO secretion may participate in this progress.