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Aims: Astragaloside IV (AS-IV) is the central active component extracted from Radix astragali, an herbal remedy widely used in traditional Chinese medicine for the treatment of cardiovascular diseases. Aberrant proliferation of vascular smooth muscle cells (VSMCs) is closely involved in the initiation and progression of cardiovascular complications, such as atherosclerosis. Here we investigated whether AS-IV inhibited agonist-induced vascular smooth muscle cells (VSMCs) proliferation and the underlying mechanism., Main Methods: Quiescent cultured A10 cells (adult rat VSMCs) were treated with Angiotensin II (AngII) or AngII plus AS-IV for 48 h. The growth rate of A10 cells was analyzed by CCK8 assay. RT-PCR analysis was carried out to examine the expression of α-smooth muscle actin (α-SMA), an important phenotypic modulation marker. In addition, whether the interference of AS-IV on AngII-mediated growth of VSMCs via regulation of cell cycle was evaluated by flow cytometry. In order to explore the role of cell cycle machinery, we measured kinase activity of CDK2 by Kinase assay and the protein level of Cdc25 by western blot, respectively., Key Findings: These data suggested that AS-IV exerted beneficial effects on AngII -induced abnormal growth in rat VSMCs through disturbing cell cycle, especially block G1/S transition by attenuating CDK2 activity, which may hinder the process of pathological vascular remodeling during atherosclerosis., (Copyright © 2018. Published by Elsevier Inc.)