Although several anticolitic drugs are available, their application is associated with numerous side effects. Here, the potential anticolitic e ciency of chicoric acid (CA; a hydroxycinnamic acid) against dextran sulfate sodium-induced colitis in rats was examined in rats. Animals were randomly assigned to the following ve groups: control, CA (100 mg/kg body weight), DSS [(DSS); 4% w/v], CA + DSS (100 mg/kg), and the 5-aminosalicylic acid (100 mg/kg) + DSS group. The obtained data revealed that CA signi cantly prevented the shortening of colon length in addition to alleviating colon histological changes in colitis rats. Meanwhile, the oxidative stress-related enzymes, in addition to malondialdehyde and nitric oxide, were markedly modulated by CA. The results also indicated that CA exerted an anti-apoptotic effect in the colitis rats by inhibiting pro-apoptogenic indices (Bax and caspase-3) and enhancing Bcl-2, the antiapoptogenic protein. Moreover, DSS caused an elevation of pro-in ammatory mediators, including interleukin-1β, tumor necrosis factor-α, myeloperoxidase, cyclooxygenase II, prostaglandin E2, and peroxisome proliferator-activated receptor gamma. Interestingly, these changes were signi cantly attenuated following the CA administration. At the molecular level, CA supplementation has increased the expression level of nuclear factor erythroid 2-related factor-2 (Nrf2) and decreased the expressions of nitric oxide synthase and mitogen-activated protein kinase 14. CA has been determined to lessen DSSinduced colitis by activating Nrf2 and its derived antioxidant molecules and suppressing in ammation and apoptosis cascades associated with the development of colitis; suggesting that CA could be used as an alternative naturally-derived anticolitic agent.