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Interleukin (IL)-22 is an IL-10 family cytokine secreted by CD4+ T cells and plays an important role in regulating inflammation and infection elimination. IL-22 homologues have been reported in the teleost, but the functions of IL-22 are still unclear. In this study, we identified two duplicated IL-22 genes in common carp (Cyprinus carpio L.), termed Cc _IL-22A and Cc _IL-22B. Sequence analysis showed that Cc _IL-22A and Cc _IL-22B had four conserved cysteine residues, which could form two intra-chain disulfide bridges. The Cc _ IL-22A and Cc _ IL-22B were constitutively expressed in various tissues, with the highest expression in the gill. The mRNA expression levels of Cc _ IL-22A and Cc _ IL-22B were significantly up-regulated in the gill, intestine, head kidney, and spleen of common carp challenged with Aeromonas. hydrophila. In vivo study showed that the expression levels of pro-inflammatory cytokines were significantly up-regulated in the head kidney and spleen when Cc _IL-22A or Cc _IL-22B were over-expressed. Furthermore, the over-expression of Cc _IL-22A and Cc _IL-22B indicated a protective effect on tissues, with only lymphocytic infiltration observed in comparison to the control and pcN3 groups, without obvious change in tissue morphology. Similar stimulatory effects of rIL-22A and rIL-22B were observed in vitro. When HKLs were stimulated with rIL-22A or rIL-22B, the expression levels of critical signaling molecules in the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway were significantly induced, including JAK1 , JAK3 , STAT1 , and STAT3 , as well as pro-inflammatory cytokines (IL-1β and TNF-α). Together, these results suggest that Cc _IL-22A and Cc _IL-22B may regulate inflammatory responses through the JAK-STAT signaling pathway and have a significant impact on the immune defense of common carp against bacterial infection. Therefore, our study provides a new perspective on the functions of Cc _IL-22A and Cc _IL-22B in the immune defense mechanism of fish. • Common carp IL-22A and IL-22B (Cc _IL-22A and Cc _IL-22B) were identified and characterized. • Cc_IL-22s widely expressed in all tested tissues and responded to bacterial infection. • In vivo , Cc _IL-22s over-expression affected the expression of inflammatory cytokines. • Recombinant Cc _IL-22s induced the expression of genes in JAK–STAT pathway. [ABSTRACT FROM AUTHOR]