Aims of study: Although the flowers of Chrysanthemurn indicum Linne (Asteraceae) have long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of a 70% ethanolic extract of C. indicum (CIE) on the activities of cellular signaling molecules that mediate inflammatory responses. Materials and methods: Production of NO, PGE(2), TNF-alpha, and IL-1 beta by ELISA, mRNA and protein expression of iNOS and COX-2, phosphorylation of MAPKs, and activation of NF-kappa B by RT-PCR and Western blotting were examined in LPS-induced RAW 264.7 macrophages. Results: The CIE strongly inhibited NO, PGE(2), TNF-alpha, and IL-1 beta production, and also significantly inhibited mRNA and protein expression of iNOS and COX-2 in LPS-induced RAW 264.7 macrophages, in a dose-dependent manner. Furthermore, the CIE clearly suppressed nuclear translocation of NF-kappa B p65 subunits, which correlated with an inhibitory effect on I kappa B alpha phosphorylation. The CIE also attenuated the activation of ERK1/2 and JNK in a dose-dependent manner. Conclusion: Our results suggest that the anti-inflammatory properties of CIE might result from the inhibition of inflammatory mediators, such as NO, PGE(2), TNF-alpha, and IL-1 beta, via suppression of MAPKs and NF-kappa B-depenclent pathways. (C) 2009 Elsevier Ireland Ltd. All rights reserved.