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This study determined the effects of chicken egg yolk antibodies (IgY) on immune responses in the intestinal mucosal of mice infected with Salmonella typhimurium. Sixty, 28-day-old mice were divided into 4 groups and treated with streptomycin or sterile water for 2 days followed by 1 day without treatment. The control group was unchallenged whereas the mice in the other three groups were treated twice with 109 CFU mL− 1S. typhimurium. For the next 3 days, control mice continued to receive no treatment whereas the mice in the remaining three groups were orally administered with 20 mg mL− 1 of specific IgY, 20 mg mL− 1 of nonspecific IgY or PBS. S. typhimurium activated gut-associated lymphoid tissue, increasing the release of IFN-γ and TNF-α in the mucosa and increased the number of activated T-lymphocytes and cytotoxic T-γδ. Specific IgY attenuated the increase in IFN-γ and TNF-α and the decrease in IL-10. S. typhimurium induced mobilization of CD8+ and CD8+ TCRγδ T cells in the epithelium and CD4+ and CD8+ T cells in the lamina propria reflecting an inflammatory process that was attenuated by IgY. These results suggest that specific IgY modulates intestinal mucosal immune responses during a S. typhimurium infection., Highlights • Specific IgY could effectively alleviate S. typhimurium-inflicted damage to the jejunum. • Specific IgY attenuated an increase in the cytokines IFN-γ and TNF-α in the mucosa. • IgY attenuated changes in lymphocyte numbers in Peyer's patches, epithelium and lamina propria. • Specific IgY has an important immune-modulatory role on the intestinal mucosal immune response. • Specific IgY limits the consequences of intestinal inflammation induced by S. typhimurium.