Aim To investigate the effect of nitric oxide (NO) on the apoptosis of cultured rat vascular smooth muscle cells (VSMC) and the role of focal adhesion kinase (FAK) in VSMC apoptosis induced by NO. Methods Flow cytometry, DNA gel electrophoresis, Northern blot and Western blot were used to determine the effect of different level of NO on VSMC apoptosis and to explore the relationship between VSMC apoptosis and expression activity of Bcl 2 and FAK genes. Results The results showed that both endogenous NO synthesized by VSMC and exogenous NO released by sodium nitroprusside (SNP) could significantly induce apoptosis of cultured rat VSMC and the apoptosis rate of VSMC was correlated with NO content in the medium. It is demonstrated that the expression activity of Bcl 2 and FAK genes markedly decreased during apoptosis development of VSMC induced by NO. Conclusions It is suggested that FAK may be involved in signal conduction of VSMC apoptosis induced by NO, and VSMC apoptosis was related to down regulation of Bcl 2 and FAK expression.