Butyrate is a bioactive molecule produced by the intestinal flora and plays a major role in a variety of inflammatory diseases. Increasing evidence indicates that butyrate can regulate the occurrence and development of atherosclerosis. Coincidentally, it reduces hyperlipidemia and hyperglycemia, which are major risk factors of atherosclerosis. However, the mechanism by which butyrate regulates the development of atherosclerosis remains unclear. In this article, we review the effect of butyrate treatment on atherosclerosis with a focus on the mechanisms of butyrate-mediated modulation of several atherosclerotic processes. These include the improvement of monocyte-endothelial interactions, macrophage lipid accumulation, smooth muscle cell proliferation and migration, and lymphocyte differentiation and function. The existing research indicates that butyrate treatment may be a potentially effective strategy for the prevention of atherosclerosis. Identity and underlying mechanisms of the molecular pathways of these interactions should be explored in the future to counter atherosclerosis effectively.This article is protected by copyright. All rights reserved.