Cirsitakaoside is a natural compound isolated from Premna szemaoensis. However, the anti-inflammatory effects of cirsitakaoside are poorly understood. We investigated the anti-inflammatory action of cirsitakaoside in lipopolysaccharide (LPS)-stimulated macrophages and mice in vivo. Cirsitakaoside could suppress the production of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in a dose-dependent manner in LPS-stimulated mouse peritoneal macrophages and RAW264.7 cells. Cirsitakaoside also could inhibit inducible nitric oxide synthase (iNOS) mRNA and cyclooxygenase-2 (COX-2) mRNA expression in LPS-stimulated mouse peritoneal macrophages and RAW264.7 cells. These effects were partially carried out by inactivated nuclear factor-κB (NF-κB) and Mitogen-activated protein kinases (MAPKs) pathway via inhibiting the phosphorylation of the IKKα/β, IκBα and c-Jun N-terminal kinase/stress-activated protein kinase (JNK) in LPS-stimulated murine macrophages. In vivo, we showed that cirsitakaoside could relieve LPS-induced inflammation response. These results suggest that cirsitakaoside has the potential anti-inflammatory effect for treatment of inflammation diseases.