Objective To study the effects of Hericium erinaceus polysaccharide on the microstructure， cytokine secretion， antioxidant function， cell proliferation and apoptosis of thymus and spleen in mice with immune stress induced by lipopolysaccharide （LPS）， so as to provide reference for the application of Hericium erinaceus polysaccharide in relieving stress.Methods Fifty male Kunming mice of 12-week old were randomly divided into control group， model group and experimental group I - III （n = 10）. In addition to the control group， the other four groups were intraperitoneally injected with 0.6 mL/kg/d LPS （once a day） three days before the end of the experiment. The experimental groups I， II and III were given 80， 160 and 320 mg/kg Hericium erinaceus polysaccharide by gavage for 2 weeks.Results Compared with the control group， the levels of interleukin-1 β （IL-1β）， interleukin-4 （IL-4） and interferon γ （IFN- γ） in thymus and spleen of mice in the model group were significantly increased （P<0.05 or P<0.01）， the activities of total superoxide dismutase （T-SOD） and total antioxidant capacity （T-AOC） were significantly decreased （P<0.05）， the content of glutathione peroxidase （GSH-Px） was also significantly decreased （P<0.05）， and the content of malondialdehyde （MDA） was significantly increased （P<0.05）. The expression of proliferating cell nuclear antigen （PCNA） mRNA in spleen of mice was significantly decreased （P<0.05）， while the expression of cysteine protease-3 （caspase-3） mRNA was significantly increased （P<0.05）. Compared with the model group， IL-1β， IL-4 and IFN-γ in thymus and spleen of mice in experimental group III was significantly higher， the activity or content of T-SOD， T-AOC and GSH Px were increased significantly （P<0.05）， and the content of MDA and the expression of caspase-3 mRNA were significantly decreased （P<0.05）. By histological observation， compared with the model group， the microstructure of thymus and spleen in experimental group Ⅲ was significantly improved， the thickness of thymic cortex was increased （P<0.01）， and the thickness of splenic nodule and periarterial lymphatic sheath was decreased （P<0.05 or P<0.01）.Conclusion Supplementation of 320 mg/kg Hericium erinaceus polysaccharide can significantly improve the damage of thymus and spleen microstructure， inhibit the secretion of pro-inflammatory cytokines and the expression of apoptosis genes induced by immune stress， and enhance the activity of antioxidant enzymes.