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The 4-week feeding experiments were conducted to investigate the effects of astragalus polysaccharides (APS) on hemocytes phagocytosis and gene expression of immune-related factors in Eriocheir sinensis—with initial weights of 6.11 ± 2.25 g. The phagocytic activity of hemocytes in E. sinensis was determined by fluorescence labeling, and the expression of immune-related factor genes in different tissues of E. sinensis was analyzed by quantitative real-time PCR (qPCR). Results showed that APS significantly improved the phagocytic activity of hemocytes in E. sinensis (p < 0.05), and the phagocytic activity of hemocytes in the 0.1% APS group was the highest (50.84%). Moreover, 0.05% APS significantly increased the expression of glutathione peroxidase (GSH-Px), anti-lipopolysaccharide (ALF), phenol oxidase (PO) and heat shock protein (HSP) genes in the hemocytes, and HSP in the hepatopancreas, and masquerade-like protein (MasL) in the gill (p < 0.05). Furthermore, 0.1% APS significantly increased the expression levels of PO, GSH-Px, ALF, MasL, and HSP genes in the hemocytes and gill (p < 0.05) and significantly increased the expression levels of PO, Crusl, and HSP genes in crab hepatopancreas (p < 0.05). In addition, 0.2% APS significantly increased the expression levels of all immune-related factor genes in the hemocytes and gill (p < 0.05) and significantly increased the expression levels of PO, ALF, Crusl, and HSP genes in the crab hepatopancreas (p < 0.05). It is estimated that APS could enhance the immune function of E. sinensis by increasing the phagocytic activity of hemocytes and the expression levels of the PO, GSH-Px, ALF, Crus1, MasL, and HSP genes. [ABSTRACT FROM AUTHOR]