In this study, the authors investigated the molecular mechanism underlying the antiinflammatory effects of the chloroform fraction of the peel of 'Jayoung' (CFPJ), a color-fleshed potato, on lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in mice with dextran sulfate sodium (DSS)-induced colitis. CFPJ inhibited the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the transcription level, and attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB depending on degradation of inhibitory κB-α (IκB-α). Furthermore, CFPJ attenuated the phosphorylations of mitogen-activated protein kinase kinases3/6 (MKK3/6) and of p38. In colitis model, CFPJ significantly reduced the severity of colitis and the productions and protein levels of pro-inflammatory mediators in colonic tissue. These results suggest that the anti-inflammatory effects of CFPJ are associated with the suppression of NF-κB and p38 activation in macrophages, and support its possible therapeutic role for the treatment of colitis.