Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammation with repeated remission and relapse. A new therapeutic strategy with no adverse effect for IBD is urgently needed. We previously found that concentration of 5,6-DiHETE, a metabolite of eicosapentaenoic acid, increased in colon tissue at healing stage of dextran sulfate sodium (DSS)-induced colitis. We further found that administration of 5,6-DiHETE inhibited vascular hyperpermeability induced by histamine. In this study, we assessed the effect of oral administration of 5,6-DiHETE on DSS colitis. Male 8 weeks old C57BL/6J mice were given 3% DSS in drinking water for 4 days. From day 9 to 14, we orally administered 150 or 600 µg/kg/day 5,6-DiHETE. DSS induced body weight loss and bloody diarrhea compared to DSS-untreated mice. Administration of 5,6-DiHETE tended to accelerate the recovery of body weight from day 9 to 14. It also tended to recover the fecal condition on day 14. Histological study revealed that DSS-treatment caused neutrophils infiltration, submucosal edema and mucosal ulceration in mouse colon on day 14. Administration of 5,6-DiHETE inhibited these changes. These results suggest that oral administration of 5,6-DiHETE accelerates recovery from DSS colitis by inhibiting the tissue edema, neutrophils infiltration and mucosal ulceration.