Perfluorooctanoic acid (PFOA), a prominent perfluorinated compound (PFC), has been widely detectat in natural water bodies worldwide. In this study, zebrafish (Danio rerio) was exposed to nominal concentrations of PFOA (0.05, 0.1, 0.5, and 1 mg/L) for 21 d. After exposure, each fish was decapitated, and the spleen was removed to detect the expression patterns of P65 transcription factor, myeloid differentiation 88, relative interleukins (ILs), and antibody genes. PFOA can stimulate pro-inflammatory cytokine at a low exposure concentration (0.05 mg/L) and can inhibit pro-inflammatory cytokine at higher exposure concentrations (>= 0.1 mg/L). The results of linear correlation analysis indicate that Myd88/NF-kappa B pathway is one of the important pathways to mediate inflammatory cytokine (IL-1 beta and IL-21) in zebrafish spleen. Additionally, the relative mRNA expression level of toll-like receptor 2 (TLR2) at 1 mg/L PFOA group was decreased to 56% of its corresponding level in the control. IL secretion disorder is possibly closely related to PFOA-induced TLR2 damage in zebrafish spleen. Furthermore, data show that the trends of PFOA-induced IL secretion have a relationship with Ig-secreting trend. This study demonstrates that PFOA can affect IL expression level through NF-kappa B, and ILs have an important function in the mediation of Ig secretion. (C) 2014 Elsevier B.V. All rights reserved.