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Growing concern for public health and food safety has prompted a special interest in developing nutritional strategies for removing waterborne and foodborne pathogens, including <i>Salmonella</i>. Strong links between manganese (Mn) and intestinal barrier or immune function hint that dietary Mn supplementation is likely to be a promising approach to limit the loads of pathogens in broilers. Here, we provide evidence that <i>Salmonella</i> Typhimurium (<i>S.</i> Typhimurium, 4 × 10⁸ CFUs) challenge-induced intestinal injury along with systemic Mn redistribution in broilers. Further examining of the effect of dietary Mn treatments (a basal diet plus additional 0, 40, or 100 mg Mn/kg for corresponding to Mn-deficient, control, or Mn-surfeit diet, respectively) on intestinal barrier and inflammation status of broilers infected with <i>S.</i> Typhimurium revealed that birds fed the control and Mn-surfeit diets exhibited improved intestinal tight junctions and microbiota composition. Even without <i>Salmonella</i> infection, dietary Mn deficiency alone increased intestinal permeability by impairing intestinal tight junctions. In addition, when fed the control and Mn-surfeit diets, birds showed decreased <i>Salmonella</i> burdens in cecal content and spleen, with a concomitant increase in inflammatory cytokine levels in spleen. Furthermore, the dietary Mn-supplementation-mediated induction of cytokine production was probably associated with the nuclear factor kappa-B (NF-κB)/hydrogen peroxide (H₂O₂) pathway, as judged by the enhanced manganese superoxide dismutase activity and the increased H₂O₂ level in mitochondria, together with the increased mRNA level of <i>NF-κB</i> in spleen. Ingenuity-pathway analysis indicated that acute-phase response pathways, T helper type 1 pathway, and dendritic cell maturation were significantly activated by the dietary Mn supplementation. Our data suggest that dietary Mn supplementation could enhance intestinal barrier and splenic inflammatory response to fight against <i>Salmonella</i> infection in broilers.