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Objective: Ulcerative colitis (UC) is characterized by mucosal inflammation and ulceration of the large intestine. Emu Oil (EO) has been reported to protect the intestine against mucositis, NSAID-enteropathy, UC-associated colorectal cancer and acute UC. We aimed to determine whether EO could reduce the severity chronic UC in mice. Methods: Female C57BL/6 mice (n = 10/group) were orally administered (gavage) water (Groups 1–2) or EO (Groups 3: low dose-80 µl and 4: high dose-160 µl), thrice weekly. Group 1 mice consumed plain drinking water throughout the trial. Groups 2–4 mice underwent two cycles [each consisting of seven days dextran sulfate sodium (DSS; 2% w/v) and 14 days water], followed by a third DSS week. All mice were euthanized two days later (day 51). Bodyweight, disease activity index (DAI), burrowing activity, myeloperoxidase activity, crypt depth and histologically assessed damage severity were assessed. p <.05 was considered significant. Results: DSS decreased bodyweight and increased DAI compared to normal controls (p <.05), which was partially attenuated by both EO doses (p <.05). Burrowing activity was impaired in DSS-controls compared to normal controls (days 27 and 40); an effect prevented by both EO doses (p <.05). DSS increased colonic myeloperoxidase activity and crypt depth compared to controls (p <.05), with no significant EO effect. Moreover, DSS increased colonic damage severity compared to normal controls (p <.001). Importantly, both EO doses decreased distal colonic damage severity compared to DSS-controls (p <.001). Conclusions: Emu Oil attenuated clinically- and histologically-assessed disease severity in a mouse model of chronic UC. Emu Oil demonstrates promise as an adjunct to conventional treatment options for UC management.