Objective: The traditional Chinese medicine Oxymatrine (OMT) has numerous biological effects, such as anti-inflammatory, anti-fibrosis, anti-proliferation and anti-tumor. However, the underlying effect of OMT on vascular smooth muscle cells remains unclear. Herein, the aim of this study is to investigate the role and mechanism of OMT on MOVAS (a mouse vascular aortic smooth muscle cell line) proliferation induced by Platelet-Derived Growth Factor-BB (PDGF-BB). Methods: Firstly, we assessed proliferation in MOVAS subjected to PDGF-BB induction or controlled intervention with/without OMT treatment. And then we detected cell cycle, cell apoptosis and the expression levels of cyclins, Cyclin-Dependent Kinases (CDKs) and p21 of each group. Results: In the present study, we found that OMT remarkably restrained the proliferation induced by PDGF-BB stimulus. Additionally, it was demonstrated that cell population of MOVAS treated with OMT in the S phase was reduced, but that of MOVAS in the G0/G1 phase was increased when compared to the PDGF-BB group. However, OMT treatment showed no effect on MOVAS apoptosis. Mechanistically, the expression of cyclinD1-CDK4/6 and cyclinE2-CDK2 were inhibited, while the expression of p21 was increased in MOVAS treated with OMT. Conclusion: These results demonstrated that the inhibitory effect of OMT on proliferation of MOVAS were in part due to G 0 /G 1 arrest by inhibiting cyclinD1-CDK4/6 and cyclinE2-CDK2, and promoting p21 expression. Therefore, OMT might become a new strategy for treating excessive proliferation of vascular smooth muscle cells in the future.