5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemother-apy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n 10; receiving saline orally for 6 d), (2) Key words mucositis; 5-fluorouracil; small intestine; rebamipide 5-Fluorouracil (5-FU) is a cytostatic agent that has been used widely in the treatment of various solid tumors for more than 20 years. It is still considered to be among the most effective anti-neoplastic agents in advanced colorectal cancer and malignancies of the head and neck.1) Many non-chromatographic and chromatographic methods for the quantitation of 5-FU, related pro-drugs, and metabolites in biological matrices have been developed over the last 30 years to support preclinical and clinical studies.2) Nevertheless, 50-80% of patients who undergo 5-FU chemotherapy show clinical manifestations of mucositis, symptoms of which include severe diarrhea.2) Its incidence in patients who underwent standarddose chemotherapy was 40%, while it approached 100% in patients treated with high-dose chemotherapy.3)The pathophysiological mechanism of 5-FU-induced mucositis comprises five phases 4)