The macrophages composed of innate immune function and acting as one of the Antigen-presenting cells.It plays important effects in body innate immune, acquired immune response, inflammation response, tissue repairing and rebuilding via secreting much cytokines.IL-21 is one of the regulatory cytokines in γc that is lately discovered which is secreted by activated CD4+ and NK cells.IL-21 activates T cell in cytokines secretion, so that to adjust the immune response.Whether IL-21 can participate the bodys inflammatory reaction by affecting the secretion of macrophages or not, no relevant reports have been seen.To investigate the effects and mechanism of IL-21 on macrophages secretory function, macrophages of BALB/C were collected and treated with LPS (100ng/mL) associated with different concentrations IL-21 (20, 100, 500 ng/mL) for 24 h.The iNOS mRNA levels of the macrophages and the protein levels of IL-6, TNF-c and IFN-γ in the cultural supernatants were detected by real-time RT-PCR and ELISA.The protein levels and phosphorylation levels of ERK, JNK, P38 and STAT3in macrophages were detected by Western blot.High levels of the iNOS mRNA in the macrophages in different concentrations IL-21 treatment were detected compared to the controls.The level of iNOS mRNA is highest when IL-21 is in 100 ng/mL.IL-21 (100 ng/mL) conspicuously decrease the protein levels of IL-6, TNF-α and IFN-γin macrophages cultural supernatants inducted by LPS but increase the phosphorylation levels of ERK, P38 and STAT3, Which indicate that IL-21 decreased the secretion of macrophage cytokines inducted by LPS through activating ERK, P38 and STAT3.