Abstract: To establish the extraction method of Agaricus blazei polysaccharides(ABP),and study the immunomodulatory effects of Agaricus blazei polysaccharides on D-galactose-induced aging mice.Agaricus blazei polysaccharides were extracted by water extraction and alcohol precipitation. The extraction process of Agaricus blazei polysaccharides was screened and optimized by single factor experiments and orthogonal experiment. The aging mouse model was constructed by D-galactose(400 mg/kg).The mice were randomly divided into 5 groups:Blank control group(CON),model group(MOD),Agaricus blazei polysaccharides low dose group(ABP-L,200 mg/kg/d),Agaricus blazei polysaccharides medium dose group(ABP-M,400 mg/kg/d),high dose group of Agaricus blazei polysaccharides(ABP-H,800 mg/kg/d). After the experiment,the thymus and spleen index of each group were determined. The proliferation and transformation of mouse spleen lymphocytes induced by ConA were determined by CCK-8 method. The contents of TNF-α and IL-6 in serum were detected by ELISA. The results showed that the optimum extraction process of Agaricus blazei polysaccharides was as follows:Extraction temperature 100 ℃,extraction time 3 h,ratio of material to liquid 1:20 g/mL,extraction times 3 times,the average yield of Agaricus blazei polysaccharides was 8.814%±0.109%.Compared with the model group,Agaricus blazei polysaccharides high dose group and ultrafine powder group significantly improved mice spleen(p<0.01)and thymus index(p<0.05),Agaricus blazei polysaccharides extremely significantly promoted spleen cell proliferation in aging mice(p<0.01),and increased TNF-α(p<0.01)and IL-6 in serum of aging mice(p<0.01).Agaricus blazei polysaccharides had immunomodulatory effect on D-galactose-induced aging mouse model.