Aim To study the effect of rhynchophylline and isorhynchophylline on the apoptosis of vascular smooth muscle cell (VSMC) induced by angiotensin Ⅱ (AngⅡ) its mechanism in rats. Methods The apoptosis model in VSMCs induced by angiotensin Ⅱ was established. The effect of rhynchophylline and isorhynchophylline on the cell morphology, apoptosis rate, [Ca2+]i concentration, Bcl-2 and Bax protein expression and mRNA expression were observed by invert phase contrast microscope, flow cytometry and RT-PCR. Results The rhynchophylline and isorhynchophylline could induce the apoptosis of VSMCs, increase cell apoptosis rate, decrease cell [Ca2+]i concentration and down regulate Bcl-2, Bax protein and mRNA expression. Conclusion The rhynchophylline and isorhynchophylline may induce the apoptosis of VSMC, whose mechanisms might be related to decreasing cell [Ca2+]i concentration and down regulating Bcl-2 and Bax protein expression and mRNA expression.