Abstract: Mechanotransduction plays an important role in the development of the cardiovascular system, the realization of physiological functions and the progress of cardiovascular diseases. Piezo1 and Piezo2 are mechanosensitive (MS) ion channels expressed in vascular endothelial cells and smooth muscle cells. Their homologous trimer structure enables them to conveniently perceive mechanical stimuli (shear stress associated with increases in local blood flow, as well as cell membrane stretch upon elevation of blood pressure). Piezo is a non-selective cation channel, mainly through Ca²⁺, and the signaling pathway downstream of Ca²⁺ plays a key role in the regulation of cardiovascular system functions, such as blood pressure regulation and vasoconstriction. We summarize the functions of Piezo in cardiovascular system and its relationship with pulmonary hypertension and atherosclerosis, in order to identify novel therapeutic strategies for the treatment of vascular diseases.