Arctigenin (ARC-G) is the main active ingredient extracted from Great Burdock Achene, with extensive pharmacological effects. In addition, ARC-G has been suggested to show excellent efficacy on inflammatory disease. This study aimed to defined that the function of Arctigenin attenuates inflammation in dextran sulfate sodium (DSS)-induced acute colitis, to determine its possible mechanism. Mice was induced by giving 2.0% DSS in the drinking water for DSS-induced acute colitis. Mice of acute colitis were injected intraperitoneally with 20 mg/kg per day of Arctigenin for 7 days. MPO activity levels were measured using MPO activity kits. Western Blot Analysis was used to determine the protein expression. Arctigenin prevents colitis and attenuates inflammation in DSS-induced acute colitis. Arctigenin suppressed NLRP3 inflammasome by SIRT1 in DSS-induced acute colitis. In THP-1 cell by LPS model, Arctigenin suppressed NLRP3, caspase-1 and IL-1β protein expression by SIRT1. Si-NLRP3 increases the effects of Arctigenin on inflammation in THP-1 cell by LPS model. Si-SIRT1 decreases the effects of Arctigenin on inflammation in THP-1 cell by LPS model. INF39, NLRP3 inhibitor also increased the effects of Arctigenin on inflammation in DSS-induced acute colitis. SIRT1 inhibitor also decreases the effects of Arctigenin on inflammation in DSS-induced acute colitis. Taken together our results demonstrated that Arctigenin attenuates inflammation in DSS-induced acute colitis through suppression of NLRP3 inflammasome by SIRT1.