Andrograpanin is a component of Andrographis paniculata, a traditional Chinese medicine (TCM) that has been effectively used for treatment of infection, inflammation, cold, fever, and diarrhea in China. Andrograpanin inhibited productions of NO and pro-inflammatory cytokines through down-regulating iNOS and pro-inflammatory cytokines gene expression levels. Further studies suggested that down-regulation of p38 mitogen-activated protein kinase (MAPKs) signaling pathways were involved in the anti-inflammatory activities of andrograpanin. This study provided evidences that andrograpanin might be useful as a potential anti-inflammatory leading compound for inflammatory drug development. Andrograpanin has the potential to modulate the chemokine pathway and the effect of andrograpanin might contribute to the anti-infectious function of A. paniculata.