Atherosclerosis (As) is a chronic inflammatory arterial wall injury process, and vessel wall cells play an important role in the occurrence and development of As. Vascular endothelial cell (VEC) act as a semi-permeable barrier between vascular smooth muscle cell (VSMC) and vascular lumen, and its injury is the initial stage of As. In addition, Through phenotypic transformation, VSMC could transform into many cell phenotype of the plaques, including macrophage, foam cell, mesenchymal stem cell and so on, and these cells further involved in the occurrence of As. Fibroblast is the main component of vascular adventitia,in pathological conditions, fibroblast differentiate into myofibroblast and participate in the occurrence of As. In this article, we will review the involvement of vascular wall cells in the mechanism of As and its potential therapeutic targets for the treatment of As, which provide new therapeutic ideas for As.