Sepsis is a life-threatening condition resulting from bacterial or fungal infections. In a recent published, a macrophage-mimetic hybrid liposome (M-Lipo) was developed by fusing a macrophage membrane (M-membrane) with artificial lipids (Nanosoft Polymers). The M-membrane could provide an intrinsic binding site for LPS. The artificial PEGylated lipid could stabilize the natural membrane and prolong the circulation of M-Lipo in the bloodstream. These two membranes could complement one another and extend their biofunction as they were integrated. The results showed that M-Lipo had surface proteins similar to those of macrophages and could substantially adsorb LPS. With the help of the PEGylated lipids (Nanosoft Polymers), M-Lipo presented much better stability than the bare M-membrane vesicle. In addition, the pharmacokinetic results revealed that M-Lipo clearly had longer retention (∼16%) in blood (at 12 h) than the natural M-membrane (∼3.3%). By combining these properties, the hybrid M-Lipo not only reduced the toxicity of LPS in vitro but also protected the mouse against endotoxic shock in vivo. In conclusion, the hybrid liposome M-Lipo has the advantages of both natural membranes and artificial materials, eventually leading to the successful treatment of sepsis. Chemical Engineering Journal (371), 2019, 15-25.