Exosomes are a type of nanoparticles in 40-200 nm extracellular vesicles secreted from living cells, containing a plurality of biologically active substances, which can be used as carriers of intercellular delivery signals. Among them, mesenchymal stem cell (MSC)-derived exosomes have been reported to play important roles in injury repair, alleviating inflammation; thus, MSC-derived exosomes have become hot spot in noncellular therapies. The role of human placental MSC-derived exosomes (hplMSC-Exos) in inflammation and their potential mechanisms are unclear. Therefore, we investigated the anti-inflammatory effects of hplMSC-Exos in lipopolysaccharide (LPS)-induced RAW264.7 cells and their intrinsic mechanisms. Our data demonstrated that hplMSCs-Exos can adjust inflammation by regulating TLR4-mediated NF-κB/MAPK and PI3K signaling pathways, indicating that hplMSCs-Exos can act as a new strategy for inflammatory treatment.