Objective To investigate the effect of paclitaxel-loaded microbubbles (PLM) triggered with ultrasound irradiation on the apoptosis of rat vascular smooth muscle cells (VSMCs) and its mechanism. Methods Rat thoracic aortic VSMCs were treated by platelet derived growth factor-BB, and then randomly divided into five groups as follows: control group (group A), microbubbles combined with ultrasound irradiation group (group B), PLM combined with ultrasound irradiation group (group C), PLM treated group (group D), and paclitaxel treated group (group E). VSMCs from groups B and C were exposed to 1 MHz continuous wave ultrasound for 120s at intensity of 0.3W/cm2. The cell cycle, apoptoitc cells and the expression of Bax and Bcl-2 were detected by flow cytometry, AnnexinV/PI staining and immunocytochemical assay, respectively. Results Compared with group A, the number of the cells arrested at S phase was decreased significantly in other groups (P＜0.01). The percentage of the cells at G0/G1 phase was greatly increased in group B, that of G2/M phase cells was increased remarkably in group D and E (P＜0.01), and those of G0/G1 phase cells and G2/M phase cells were increased significantly in group C (P＜0.01). Apoptosis rate was significantly higher in group B and C than in group A (P＜0.01), while the expression of Bax was increased, and that of Bcl-2 decreased (P＜0.01). Conclusion Ultrasound triggered PLM induces rat VSMCs apoptosis, which might be due to upregulation of Bax and downregulation of Bcl-2 induced by microbubbles-mediated ultrasound cavitation.