|Cyanidin-3β-D-glycoside (C3G), which is widely distributed in herbal medicines and functional foods, exhibits anti-inflammatory, anti-oxidant, and anti-scratching behavioral effects. Orally administered C3G is metabolized to protocatechuic acid (PA) by gut microbiota. Therefore, we compared the anti-colitic effect of C3G to that of PA in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Orally administered C3G and PA preventively and curatively ameliorated TNBS-induced colitis parameters, including macroscopic colitis score, colon shortening, and increase of myeloperoxidase activity. Treatment with C3G or PA also inhibited the expression of cyclooxygenase-2, inducible NO synthatase, IL-1β, IL-6, and TNF-α and the activation of NF-kB in the colon of mice with TNBS-induced colitis. Furthermore, these also inhibited lipopolysaccharide-induced NF-kB activation and TNF-α expression in peritoneal macrophages. The anti-colitic effect of PA was more effective than C3G. Orally administered PA more potently attenuate colitis than C3G by inhibiting NF-kB activation and the anti-colitic efficacy of C3G may be dependent on the biotransformation of C3G to PA by gut microbiota.