The hypothesized portrait of fish gut-liver immunity was drawn accordingly to the discussion of current revealed immune genes in tilapias’ gut and liver. Besides immune components at both intestinal mucosal barrier and liver reticulo-endothelial system, intestinal mucus and bile also contain many immune modulators or activators. During immune homeostasis, on one hand, in gut, genes of possible immunomodulatory role, including innate immune molecules, such as galectin and c-type lectin, as well as regulatory T/B cell related ones, together with genes responsible immune-suppression, such as IL1R, were found with abundance. On the other hand, in liver, in addition to immunomodulatory and immune suppression genes, innate immune molecules, such as acute phase proteins, complement components and anti-microbial peptides, which could be delivered from bile to intestinal mucus, were found of great importance for basic function. In addition, molecules (chemokines and integrins, with some members different from mammals) related to migration of lymphocytes between gut and liver were also inferred particular at steady state (termed homing). While upon inflammation, in gut, the immune genes, responsible for immune activation, including both innate ones, such as fish-egg lection (fish-specific), CFD and C1q, and adaptive ones, mainly T cell response (CD8+T, Th1 and Th17) related, were prevailing. At the same time in liver, genes for activation of immune responses, mainly including innate immune molecules and cells, together with relative lower T cell response, were found. Innate immune factors could be also transported from bile to intestinal mucus upon inflammation. Genes labeled or related to immune cells in the diagram were all highlighted in Tables S6 and S7.