OBJECTIVE Garlic oil (GO) is used for centuries in folk medicine as a therapy for many diseases including inflammatory disorders. Recently, it has exhibited potent anti-oxidant, anti-inflammatory and immunomodulatory effects. Consequently, we evaluated the possible protective effect of GO in a rat model of colitis, induced by dextran sulfate sodium (DSS). METHODS Colitis induced by allowing rats a free access to drinking water containing 5% DSS for 7 days, from day 1 to day 7. GO was administered orally in doses of 25, 50 and 100mg/kg/day. Mesalazine used as a standard medication in a dose of 15 mg/kg/day. All animals fasted for 2h, 1h before and 1h after giving the treatment, which introduced daily for 7 days, from day 1 to day 7, at 10:00 to 11:00 A.M. Animal body, and colonic weights, colonic myeloperoxidase (MPO), and superoxide dismutase (SOD) activities, colonic reduced-glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-10 levels, macroscopic and microscopic changes of colonic tissues were evaluated. RESULTS GO treatment significantly suppressed the elevated colonic weight, MPO activity, MDA, TNF-α and IL-1β levels. However, it potentiated the decrease body weight, colonic SOD activity, GSH and IL-10 levels. Moreover, it ameliorated the marked macroscopic and microscopic changes of colonic mucosa in a dose dependent manner. CONCLUSIONS Garlic oil inhibits DSS-induced colitis in rats may be through its anti-oxidant, anti-inflammatory and immunomodulatory properties. Therefore, GO could be a promising protective agent recommended for UC patients.