Activin A is a multifunctional factor of the transforming growth factor-beta (TGF-beta) superfamily and acts as an anti-inflammatory cytokine produced by microglia and macrophages. In this study, we investigated the regulatory effect and possible mechanism of activin A on activation of lipopolysaccharide (LPS)-induced mouse peritoneal macrophages. The results showed that activin A could decrease NO release in LPS-activated mouse peritoneal macrophages, and suppressed phagocytosis and pinocytosis of mouse peritoneal macrophages stimulated by LPS in vitro and in vivo. Furthermore, activin A remarkably inhibited the expressions of CD14 and MHC II on LPS-induced mouse peritoneal macrophages, but had no significant effect on the expression of MHC I and the proliferation of mouse peritoneal macrophages. These findings suggest that activin A can down-regulate inflammatory mediator production and phagocytosis of LPS-activated macrophages via suppressing CD14 expression, and may influence the presentation of exogenous antigens via inhibiting MHC II expression. Thus, activin A might have the potential for treatment of macrophage-mediated inflammatory diseases through modulating both innate and adaptive immune responses.