In the present study, an antibody highly specific to the Nile tilapia (Oreochromis niloticus) Foxp3 was produced and characterized Immunohistochemistry analysis indicates that Foxp3 was expressed in peripheral blood mononuclear cells (PBMC) and certain packed lymphocytes in particular, whats more, the percentage of Foxp3+ cells among PBMC was 5 7±2 0% (n=5) in healthy adults and could be significantly up-regulated after phytohemagglutinin (50 μg/mL) stimulation in vitro at 6, 12 and 24 h, respectively In the lymphoid tissues, such as the thymus, spleen and head kidney, Foxp3 expression was observed mainly in lymphocyte-like cells Surprisingly, in the non-lymphoid organ stomach, Foxp3 was detected in epithelial-like cells within the mucosa Our sthdy demonstrates for the first time that Foxp3 protein expression occurs not only in hematopoietic cells of lymphoid organ systems but also non-hematopoietic cells of non-lymphoid organ in lower vertebrates such as the fish tilapia The conserved expression pattern of Foxp3 at the protein and cellular levels implies that it might have conserved functions from fish to mammals.