LPS, an endotoxin isolated from gram-negative bacterial, has been shown to be a potent cytokine initiator in murine peritoneal macrophages. CAMP-dependent pathway is generally considered to play a suppressive role in immune response. This study investigated the effect of cAMP on LPS-induced gene expression of cytokines in murine macrophages. Our data clearly demonstrated that in LPS-treated macrophages, cAMP elevator (CTx and 8-bromo-cAMP) could increase IL-1Ra and IL-10 gene expression, while mRNAs of IL-1 alpha, IL-12, IL-6, and MIF were decreased and other cytokines Like IL-1 beta, and IFN-gamma did not give a definite tendency. This is the first report that CTx and 8-bromo-cAMP positively regulate IL-1Ra gene expression in LPS-stimulated macrophages. Our data also suggest that a cAMP-dependent pathway may play a regulatory role in Toll-receptor system.