Omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) are known to have strong anti-inflammatory effects. In the present study, we investigated the protective effects of omega-3 PUFAs on experimentally induced murine colitis. Intrarectal administration of 2.5% 2,4,6-trinitrobenzene sulfonic acid (TNBS) caused inflammation in the colon of wild type mice, but this was less severe in fat-1 transgenic mice that constitutively produce omega-3 PUFAs from w-6 PUFAs. The intraperitoneal administration of docosahexaenoic acid (DHA), a representative omega-3 PUFA, was also protective against TNBS-induced murine colitis. In addition, endogenously formed and exogenously introduced omega-3 PUFAs attenuated the production of malondialdehyde and 4-hydroxynonenal in the colon of TNBS-treated mice. The effective protection against inflammatory and oxidative colonic tissue damages in fat-1 and DHA-treated mice was associated with suppression of NF-kappa B activation and cyclooxygenase-2 expression and with elevated activation of Nrf2 and upregulation of its target gene, heme oxygenise-1. Taken together, these results provide mechanistic basis of protective action of omega-3 fatty PUFAs against experimental colitis. (C) 2017 Published by Elsevier Inc.