Sepsis is a severe immune response to pathogens that is associated with high mortality rate and a paucity of efficacious treatment options. It is characterized by the hyperactivation of macrophages and the occurrence of cytokine storms. Given the anti-inflammatory properties of M2 macrophages and their derived apoptotic bodies (AB), as well as the specific uptake of these by macrophages, a novel approach was employed to combine AB with artificial liposomes to create apoptotic body based biomimetic hybrid nanovesicles (L-AB). The L-AB effectively inherited "eat me" signaling molecules on the surface of the AB, thereby facilitating their targeted uptake by macrophages in both in vitro and in vivo settings. The administration of L-AB for the delivery of dexamethasone effectively augmented the therapeutic efficacy of the drug, mitigated macrophage hyperactivation and tissue damage in vivo, and consequently enhanced the survival rate of septic mice. Taken together, these findings suggest that the apoptotic body biomimetic nanovesicles may represent a potential drug delivery system capable of specifically targeting macrophages for the treatment of sepsis.