Sugiol is a diterpene which was isolated and purified from alcohol extracts of the bark of Calocedrus formosana Florin (Cupressaceae). Although sugiol has low inhibitory activity against the DPPH radical, it could effectively reduce intracellular reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated macrophages. The present study investigated the potential anti-inflammatory activity of sugiol, and the relationship between signal transduction and inflammatory cytokines in vitro. A dose of 30 microM of sugiol was effectively inhibitory for proIL-1beta, IL-1beta and TNF-alpha production, suggesting that sugiol is bioactive against inflammation. Moreover, sugiol reveals a capacity for suppressing the activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) activated by LPS-stimulation in J774A.1 murine macrophages. A low dosage of 10 microM of sugiol completely inhibited ERK1/2 phosphorylation, while 30 microM effectively inhibited JNK1/2 and p38 phosphorylation in LPS-stimulated macrophages. In addition, sugiol significantly inhibited LPS-induced ROS production. Our studies suggest that sugiol's efficacy in inhibiting the inflammatory cytokines of IL-1beta and TNF-alpha could be attributed to a reduction of the ROS that leads to a decrease in the phosphorylation of MAPKs.