Atherosclerosis (As) is an important pathological basis for cardio-cerebrovascular diseases. In recent years, many studies have shown that epigenetic mechanisms also play an important role in the regulation of As. 5-hydroxymethyl cytosine (5hmC), known as the sixth base of human DNA, is an important epigenetic modification derived from the demethylation process of DNA mediated by the ten-eleven translocation (TET) protein family, and has been known to involve in various biological processes. Recent studies have shown that TET2 and its mediated hydroxymethylation are not only involved in the regulation of phenotypic transformation of vascular smooth muscle cells, but also closely related to the key factors of As such as endothelial function and inflammatory immune response. It is also found that TET2 and 5hmC are markedly absent in As plaque, and the level of deletion is positively correlated with the degree of injury. TET2 and hydroxymethylation may play an important protective role in the pathological process of As. This review will introduce the structure and function of TET2, the research overview of 5hmC and the breakthrough in detection techniques. It will focus on the role and mechanism of TET2 and its mediated hydroxymethylation modification in As, and provide new ideas and targets for the effective prevention and treatment of As.