Abstract: Macrophages, as the main effector cells of innate immune response, exist in all tissues in the body, has become a new target of immunotherapy because of their high plasticity. Lipid droplets are storage organelles related to fat metabolism and energy homeostasis, but they are not simple lipid reservoirs, but multi-functional organelles with active metabolism. Recent studies have found that lipid droplets, as a hub integrating metabolism and inflammation, play a central role in the regulation of macrophage inflammatory phenotype. This article reviews the relationship and regulation mechanism between macrophage inflammatory phenotype and lipid droplet loading. Based on the regulation and main mechanism analysis of lipid droplet loading on macrophage inflammatory phenotype in atherosclerosis, tumor, tuberculosis and other inflammatory diseases, it discusses the therapeutic potential of regulating targeted lipid droplet loaded macrophages in the treatment of inflammatory diseases.