Chrysophanol is a member of the anthraquinone family and has multiple pharmacological effects, but the exact mechanism of the anti-inflammatory effects of chrysophanol has yet to be thoroughly elucidated. In this study, we attempted to determine the effects of chrysophanol on dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. The findings of this study demonstrated that chrysophanol effectively attenuated overall clinical scores as well as various pathological markers of colitis. Additionally, chrysophanol inhibited the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and the expression of cyclooxygenase (COX)-2 levels induced by LPS. We showed that this anti-inflammatory effect of chrysophanol is through suppression of the activation of NF-kappaB and caspase-1 in LPS-stimulated macrophages. These results provide novel insights into the pharmacological actions of chrysophanol as a potential molecule for use in the treatment of inflammatory diseases.