Increased levels of pro‐inflammatory lipid mediators called prostaglandins (PGs), particularly PGE2 in patients with active ulcerative colitis (UC) indicates its critical role in inflammatory bowel disease (IBD). Therefore, resolving inflammation by therapeutic strategies that can reduce PGE2 levels are promising to treat UC. Recently, we have reported that Se as a part of redox regulatory proteins can resolve inflammation by modulating the cyclooxygenase‐2 (COX‐2) dependent PG synthesis pathways. The aim of the present study is to dissect the redox sensitive inflammatory metabolic pathways leading to PGE2 inactivation that can help in the resolution of inflammation. Currently, we demonstrated that in a DSS induced experimental colitis model Se supplementation (0.4 and 1.0ppm), which is above the adequate limits (80ppb), completely relieved the classical signs of colitis‐associated inflammatory markers such as TNF‐α, IL‐1β and IFN‐γ. A concomitant increase in the expression of 15‐PGDH in the colons of these mice indicated that Se by regulating the metabolic pathways of pro‐inflammatory PGs can mitigate the inflammatory processes in IBDs. Studies in macrophage‐selenoproteins specific genetic knockouts indicated their critical role in activating resolution pathway of inflammation. Current study addresses the central role of redox equilibrium in the inflammatory processes associated with UC and the approaches to manipulate these redox networks to treat IBD. Understanding the role of Se in the resolution of inflammation and the molecular mechanisms underlying such protective effects of functional foods can be used as an adjunct therapy in colitis.Grant Funding Source: NIH