Atherosclerosis (As) is closely related to lipid metabolism disorder and inflammation. The current study shows that intestinal microbial flora is also involved in the As process and is one of the independent risk factors of As.The human gut is the largest digestive organ and “the largest immune organ” of the body. Normal intestinal flora participates in bile acid metabolism, and the short-chain fatty acids produced by bacterial metabolism inhibit inflammation, thus suppressing As. Unbalanced intestinal flora affects trimethylamine metabolic pathway of the host, disturbs the metabolism of cholesterol in the body, triggers the innate and adaptive immune responses, and attenuates the protective effect of anti-inflammatory, thus promoting As. Therefore, the regulation of unbalanced intestinal flora becomes a new target for the treatment of As. This article will review the immune mechanism of intestinal flora affecting As.