Abstract Salvia miltiorrhiza (SM) has been commonly used in traditional medicine to treat vascular diseases such as hypertension, arteriosclerosis, and inflammatory disease. It is little kwon that extract of SM alters the immune response of inflammatory reaction. Macrophage, essential cellular components of the body's host defense system, has critical functions in both innate and adoptive system. Macrophages exhibit a particularly vigorous response to endotoxin, which induces production of a variety of inflammatory mediators, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostagrandinE2 (PGE2), and nitric oxide (NO) via the inducible nitric oxide synthase (iNOS). In this study, we examined that inhibition effect of ethanol extract of SM (ESM) on pro-inflammatory mediators in LPS-induced murine macrophage cell line RAW 264.7 cells as well as in primary macrophages. ESM deceased the production NO and pro-inflammatory cytokine such as IL-1β, IL-6, TNF-α, and COX-2 in LPS-stimulated macrophage. The variation of gene expression level by ESM treatment was determined by RT-PCR and the relation of mRNA expression of pro-inflammatory cytokine in activated macrophage was suppressed by ESM. In western blot analysis, the level of cytokine protein was decreased in activated macrophage by ESM dose-dependently manner. In addition, the expression of co-stimulatory molecules such as ICAM-1, B7-1, and B7-2 was decreased by ESM dose-dependently. These results showed that ESM has immunomodulatory activities in both innate and adoptive immunity, and they provide the critical information for the understanding of the mechanism of inflammation studies. Key words: Salvia miltiorrhiza, anti-inflammatory, immunomodulator, cytokines