In recent years, many studies found that there commonly existed atherosclerotic plaque neovascularization, and it might promote the progression of the plaque and even cause plaque hemorrhage and rupture. Thus, plaque neovascularization is an important mechanism that turns stable plaques to vulnerable ones. Early identification of vulnerable plaques has been a key and difficult point in clinical practice. CD105, a glycoprotein expressed in endothelial cells, is a member of the transforming growth factor-β superfamily, and is considered as an ideal indicator of human endothelial proliferation. In this review, we summarized the molecular structure and function of CD105, the relationship between this molecule and plaque neovascularization, and the significance and recent progress in anti-angiogenesis for the treatment of atherosclerosis.