A variety of anti-inflammatory agents have been shown to exert chemopreventive activity via targeting of transcription factors such as NF-${kappa}B$ and AP-1. Lithospermum erythrorhizon (LE) has long been used in traditional oriental medicine. In this study, we demonstrated the inhibitory effects of LE extracts on lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines. As an underlying mechanism of inhibition, LE extracts reduced LPS-induced transactivation of AP-1 as well as NF-${kappa}B$ in mouse macrophage cells. Electrophoretic mobility shift assays indicated that LE extracts inhibited the DNA binding activities of AP-1 and NF-${kappa}B$. In addition, phosphorylation of $I{kappa}B-{alpha}$ protein was suppressed by LE extracts. Moreover, LE extracts inhibited c-Jun N-terminal kinase and extracellular signal-regulated signaling pathways. Our results suggest that the anti-inflammatory activity of LE extracts may be mediated by the inhibition of signal transduction pathways that normally lead to the activation of AP-1and NF-${kappa}B$. These inhibitory effects may be useful for chemoprevention of cancer or other chronic inflammatory diseases.