Background Autologous fat grafting has become a popular tool in plastic surgery to solve soft tissue defects and achieve skin rejuvenation, but the volume loss after transplantation remains a disturbing problem. In recent years, some new strategies have improved the outcome to some extent, but the fat graft retention is still far from ideal, so there remains a wide development prospect in this field. Macrophages are closely related to the local microenvironment and tissue regeneration, and their role in fat grafting has been increasingly highlighted. Aims This article was aimed to review the efficacy, possible mechanisms, and potential application of macrophage regulation on fat grafting, as well as concerns and future perspectives of this filed. Methods A retrospective review of the published data was conducted. Results Most studies indicated that up‐regulating M2 macrophages during fat grafting would improve fat retention via promoting neovascularization. M2 macrophages could secrete several pro‐angiogenic factors, accelerate extracellular matrix (ECM) remodeling, and directly function on endothelial cells to encourage vascular expansion. In addition, macrophages could influence the proliferation, apoptosis, and adipogenic differentiation of preadipocytes. Conclusions During autologous fat grafting, appropriately regulating macrophages may become a promising method to increase fat retention. Nevertheless, the M2 macrophage polarizing agents, treatment opportunity, and contraindications require further discussion. We hope our work could promote more in‐depth studies in this field, and we are looking forward to a standard procedure for the macrophage therapy in clinical practice.