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Edwardsiella tarda is a Gram-negative bacterial pathogen with a broad range of hosts, including fish and mammals. In the present study, we used an advanced antibody array technology to identify the expression pattern of cytokines induced by E. tarda in a mouse infection model. In total, 31 and 24 differentially expressed cytokines (DECs) were identified in the plasma at 6 h and 24 h post-infection (hpi), respectively. The DECs were markedly enriched in the Gene Ontology (GO) terms associated with cell migration and response to chemokine and in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with immunity, diseases, and infection. Ten key DECs, including IL6 and TNF-α, were found to form extensive protein-protein interaction networks. IL6 was demonstrated to inhibit E. tarda infection and be required for E. tarda-induced inflammatory response. TNF-α also exerted an inhibitory effect on E. tarda infection, and knockdown of fish (Japanese flounder) TNF-α promoted E. tarda invasion in host cells. Together, the results of this study revealed a comprehensive profile of cytokines induced by E. tarda, thus adding new insights into the role of cytokine-associated immunity against bacterial infection and also providing the potential plasma biomarkers of E. tarda infection for future studies. [ABSTRACT FROM AUTHOR]