INTRODUCTION: Chlorogenic acid (CHA) is a common polyphenol prevalent in human diet since is contained in various foods and beverages. Ulcerative colitis (UC) a subtype of inflammatory bowel disease is a long-lasting, relapsing and non-specific inflammatory disorder of a gastrointestinal tract. There is substantial indication to show that CHA exhibit many biological properties, including antioxidant and anti-inflammatory effects. However, its impact on experimental colitis is still unidentified. AIM: Therefore, we investigated the potential protective and therapeutic effect of CHA administration in dextran sulfate sodium (DSS)-induced mouse model of experimental colitis. MATERIALS AND METHODS: Experimental acute colitis was induced by administration of 2.5% dextran sulfate sodium (DSS) in the drinking water of C57BlL/6 mice for seven days. Mice received CHA at dose of 100 and 200 mg/kg, per os once a day from day three to seven when they had been sacrificed. The disease activity index, colon length, histological assessment, expression of nuclear factor-kappa B (NF-κB) and p-IκBα were examined. RESULTS: Oral administration of CHA at a dose of 100 mg/kg and 200 mg/kg significantly attenuated the disease activity index, colon shortening and histological damage. In addition, oral administration of CHA at a dose 200 mg/kg/day decreased the expression of nuclear transcription factor p-IκBα. Furthermore, immunohistochemical analysis showed a dose-dependent decrease in expression of NF-κB p65 subunit. CONCLUSION: These observations designate that CHA may suppress experimental colitis through the NF-κB signalling pathway