Phosphatidylserine (PS) mimics the anti-inflammatory effect of apoptotic cells by binding to the PS receptor of macrophages. In this study, the effect of PS-modified polylactide-co-glycolide (PLGA) nanoparticles on macrophage polarization was investigated.PLGA nanoparticles (PLGAnPs) containing phosphatidylcholine (PC) and PS were prepared using the emulsificationsolvent-evaporation (ESE) technique and classified as follows: 1) PC 100% (PCnP); 2) PS:PC = 50:50 (PSPCnP); and 3) PS 100% (PSnP). PS-grafted PLGAnPs tended to inhibit LPS-induced morphological change into M1 macrophages and mRNA expression of the M1 markers (TNF-α, IL-1β, IL-6, IL-12p40, CD86, and iNOS). In particular, the expressions of TNF-α, IL-6, and IL-12p40 were significantly decreased in the PSPCnP group, as compared to those of the positive control and and PLGAnP groups (p<0.05). Therefore, the study results demonstrate the potential of PS-grafted PLGAnPs in attenuating inflammation and modulating the drug delivery system.