Schizonepeta tenuifolia (ST) is a well-known herb to treat the cold and its associated headache. However, the anti-inflammatory mechanism of ST in mouse peritoneal macrophages is not clear. In study, It demonstrated that ST inhibited lipopolysaccaride (LPS)-induced tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production. The maximal inhibition rate of TNF-alpha and IL-6 production by ST (2 mg/ml) was 48.01 +/- 2.8% and 56.45 +/- 2.8%, respectively. During the inflammatory process, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were increased in mouse peritoneal macrophages. However, treated with ST decreased the protein level of COX-2 and iNOS, as well as the production of PGE(2) and NO in LPS-stimulated mouse peritoneal macrophages. In addition, ST inhibited the phosphorylation of MAPK. Schizonepeta tenuifolia  has been used for the treatment of skin disorders, allergic dermatitis, eczema, and inflammatory diseases.