<p>Allogeneic skin transplantation is a critical method for treating extensive burns, trauma, and skin defects; however, its success is severely limited by immune rejection, driven by complex interactions between innate and adaptive immunity. Macrophages, particularly their polarization states, play pivotal yet dual roles in this process. While M1 macrophages exacerbate inflammation and graft damage, M2-polarized macrophages emerge as critical regulators of immune tolerance. Manipulating macrophages to polarize into M2 can not only reduce graft rejection but also induce immune tolerance, thereby promoting graft survival. M2 macrophages effectively inhibit transplant rejection by secreting anti-inflammatory cytokines, suppressing T-cell activation, and fostering the differentiation of immunosuppressive cells. This review delineates the immunological basis of skin allograft rejection, the intrinsic mechanisms governing M2 polarization, and the role of M2 macrophages in inducing immune tolerance in allogeneic skin transplantation. The discussion provides a theoretical foundation for novel immunosuppressive strategies and underscores M2 macrophages as therapeutic targets to improve transplant outcomes, bridging mechanistic insights to clinical innovation. Safer and more effective immunomodulatory strategies are anticipated to increase the success rate of allogeneic skin transplantation and enhance patient quality of life.</p>