Abstract: The phenotype of vascular smooth muscle cells (VSMCs) is highly plastic. Influenced by hypoxia, inflammation or some other factors, VSMCs often switch from a contractile into a secretory phenotype, which shows that the cell contractility is weakened, while their abilities of proliferation, migration and secretion are significantly enhanced. The phenotypic switch plays an important role in regulating the progression of multiple vascular diseases, such as atherosclerosis and pulmonary arterial hypertension. Previous studies have shown that the phenotypic switch of VSMCs is regulated by a variety of factors, such as microenvironment cytokines, metabolic remodeling signaling pathways, extracellular matrix and biological forces and targeted regulation of these molecules and signaling pathways can effectively improve the course of vascular diseases. Therefore, the mechanisms of phenotypic switch of VSMCs and its role in the progression of vascular diseases will be described in this review, in order to provide a theoretical basis for the clinical treatment of vascular diseases.