In conclusion, our work identified MFG-E8-mediated protective mechanism of wound injury in diabetes, including: (i) suppression of activated NLRP3 inflammasome targets IL-1β/IL-18 synthesis; (ii) attenuation of NETs release from neutrophils induced by inflammatory cytokine IL-1β/IL-18; (iii) might control NET-primed NLRP3 inflammasome activation through integrin β3 and limiting P2X7 receptor; (iv) enhancement of angiogenesis in wound bed. Here, P2RX7 is linked to diabetes mellitus.