Objectives : Samhwangsashim-tang(SHSST), a mixture of Rhei radix et rhizoma, Scutellariae radix, and Coptidis rhizoma, has been regarded as being able to treat bleeding, gastric discomfort, dry mouth, insomnia and purpura due to Blood Heat. Currently, this herbal formula is applied to gastritis, gastric ulcer, hypertension, atherosclerosis or other types of vascular inflammatory disorders. Methods : We extracted this herbal mixture with 30% ethanol and examined for its effects on systemic inflammatory responses and in vitro macrophage activity. Mice were orally given to SHSST for 7 days and then lipopolysaccharide(LPS) was intraperitoneally injected. Tumor necrosis factor-${alpha}$(TNF-${alpha}$) levels in serum were measured 1 h after LPS challenge. Peritoneal macrophages were isolated from thioglycollate-injected mice and used for in vitro cellular activity. Cell death was measured using the MTT method and annexin V/propidium iodide staining. LPS-stimulated signaling molecules necessary for TNF-${alpha}$ expression were determined by Western blotting. Results : Oral administration of SHSST for 7 days resulted in a significant reduction in LPS-stimulated TNF-${alpha}$ release into serum. In vitro treatment of SHSST was cytotoxic in a concentration-dependent manner. However, SHSST caused a concentration-dependent reduction in necrosis and increase in apoptosis in mouse peritoneal macrophages. SHSST inhibited the activation of NF-${kappa}B$, p38 and JNK signaling molecules in response to LPS. Conclusion : Taken together, our results demonstrated that SHSST was effective in lowering LPS-stimulated TNF-${alpha}$ serum levels, possibly through its modulation of NF-${kappa}B$, p38 and JNK in macrophages.