Resolution of inflammation is a key physiological process regulated at different levels, and failure to achieve resolution may result in chronic inflammation. In this issue of Blood , Sugimoto et al reveal the function of the plasmin system in resolving inflammation by inducing macrophage polarization toward M2 and proresolving phenotypes. Plasmin-derived M2 macrophages produce 2 key effector processes for the resolution of inflammation: annexin A1 and neutrophil efferocytosis. 1