This study aims to explore the role and mechanism of Cordyceps polysaccharides (CSP) in improving macrophage efferocytosis function based on peroxisome proliferator-activated receptor γ(PPAR-γ).The CSP was extracted by hydro-alcohol precipitation.The molecular weight distribution,monosaccharide composition and methylation products of CSP were detected by high performance liquid gel chromatography,PMP-high performance liquid chromatography and methylation analysis,respectively.The effects of CSP on mouse macrophage cell viability,efferocytosis-related genes and efferocytosis rate were determined by CCK-8 assay,real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and flow cytometry,respectively.The effect of CSP on PPAR-γ expression and nuclear localization was observed by immunofluorescence.Si-RNA was then used to knock down PPAR-γ to verify the possible target genes and signaling pathways of CSP.The results showed that the CSP contained 72.9% polysaccharides,with a molecular weight distribution of 21.9,2 100 kDa and more than 50 000 kDa.The CSP was mainly composed of glucose,galactose and mannose,and it contains six main glycosidic bonds.Compared with the model group,CSP increased the expression of efferocytosis-related genes TAM receptor tyrosine kinase (Tyro3/Axl/Mer receptor tyrosine kinase,TAM),milk fat globule-epidermal growth factor 8 (Mfge8) and the efferocytosis rate of macrophages (P<0.05).Meanwhile,CSP promoted the protein expression of PPAR-γ (P<0.001) with nuclear translocation.In addition,the ability of CSP to promote the expression of macrophage efferocytosis-related genes was significantly affected after knockdown of PPAR-γ (P<0.05).Our study suggests that CSP may enhance oxidized low-density lipoprotein (ox-LDL)-induced macrophage efferocytosis through activating PPAR-γ signaling pathway.