The purpose of this study was to investigate the anti-inflammatory effects and cellular mechanism of piperine on murine peritoneal macrophages. To evaluate the effects of piperine, we examined the production of nitric oxide (NO), interleukin (IL)-10 and IL-12. To investigate inhibitory mechanism of piperine, we examined the MAPKs and Ik-Ba in murine peritoneal macrophages, Piperine itself does not have any cytotoxic effect and reduced lipopolysaccharid (LPS), Poly(I:C), CpG-ODN -induced production of NO, IL-10 and IL-12 in peritoneal macrophages. Piperine inhibited the activation of extracelluar signal-regulated kinase (ERK 1/2) and c-Jun NH2-terminal kinase (JNK 1/2) not the activation of p38 and the degradation of inhibitory kappa B a (Ik-Ba) in the LPS-stimulated murine peritoneal macrophages.ln conclusion, Piperine down-regulated LPS-induced production of NO, IL-10 and IL-12, which could provide a clinical basis for anti-inflammatory properties of piperine.