Objective:　Ulcerative　colitis　(UC)　is　one　of　the　most　common　gastrointestinal　diseases,　characterized　as　a　chronic,　relapsing　inflammation　that　causes　damage　to　the　colonic　mucosa.　Maresin　1　(MaR1),　a　specialized　proresolving　mediator,　has　powerful　anti-inflammatory　activity　that　prevents　the　occurrence　of　various　inflammatory　diseases.　The　aim　of　this　study　was　to　explore　the　role　and　potential　mechanism　of　MaR1　in　DSS-induced　ulcerative　colitis.　Methods:　In　the　present　study,　we　established　dextran　sulfate　sodium　(DSS)-induced　ulcerative　colitis　rat　model　in　vivo.　Rats　with　colitis　received　tail　vein　injection　of　MaR1,　with　or　without　intraperitoneal　injection　of　ML385.　The　changes　of　body　weight,　colon　length,　disease　activity　index　(DAI),　colonic　histopathology,　inflammatory　cytokines,　the　activity　of　myeloperoxidase　(MPO)　and　reactive　oxygen　species　(ROS),　and　infiltration　of　macrophages　expressing　F4/80　were　analyzed　for　the　evaluation　of　colitis　severity.　In　addition,　protein　expressions　were　detected　using　western　blot.　Results:　MaR1　significantly　reduced　inflammatory　cytokines　production,　and　restored　body　weight,　DAI　and　colonic　histopathology.　Besides,　MaR1　improved　the　expression　of　tight　junction　(TJ)　proteins　and　reduced　the　infiltration　of　neutrophil　and　macrophages,　as　well　as　a　decreased　activity　of　MPO　and　ROS.　Meanwhile,　MaR1　activated　Nrf2　signaling　and　decreased　toll-like　receptor　4(TLR4)/nuclear　factor-kappa　B(NF-kappa　B)　activation.　Furthermore,　ML385,　an　inhibitor　of　Nrf2,　significantly　reversed　the　protective　effect　of　MaR1.　Conclusion:　MaR1　play　a　protective　role　in　DSS-induced　colitis　by　activating　Nrf2　signaling　and　inactivating　Nrf2-mediated　TLR4/NF-kappa　B　signaling　pathway,　which　mediate　proinflammatory　mediators　and　intestinal　TJ　proteins　in　rats,　providing　novel　insights　into　the　therapeutic　strategy　of　colitis.