This study aims to investigate the effects and underlying mechanisms of Astragalus polysaccharide (APS) in enhancing resistance to Staphylococcus aureus (SA) infection in mice. Mice were administered APS at dosages of 100 mg/kg and 400 mg/kg for a duration of 14 days, followed by exposure to SA at a concentration of 1×10⁹ CFU/mL to establish a bacterial infection model.The impact of SA infection was assessed by monitoring general physiological changes in the mice,quantifying bacterial load in visceral organs, and measuring serum levels of inflammatory markers.Additionally, histopathological alterations in the small intestine were examined using hematoxylin-eosin staining.The mucous composition of colonic tissue was visualized using alcian blue staining.Detection kits were employed to quantify the fecal bacterial load,as well as the levels of secretory immunoglobulin A (SIgA) and mucin2 (MUC2) in both fecal and intestinal fluid samples.The findings demonstrated that APS markedly diminishes the organ burden of SA-induced bacterial infections in mice,elevates fecal load,and decreases serum concentrations of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β).Additionally,APS enhances the serum level of the anti-inflammatory cytokine interleukin-10 (IL-10),thereby exerting a significant impact on small intestine tissue injury.Furthermore,APS significantly promotes the secretion of MUC2 in colonic tissue,leading to increased levels of SIgA and MUC2 in both feces and intestinal fluid.The aforementioned findings suggest that APS can augment the resistance of experimental animals to pathogenic microbial infections.This mechanism appears to be associated with the enhancement of intestinal mucosal immunity and barrier function facilitated by APS.