[Background] Serious oral stomatitis reduces the quality of life of 5-fluorouracil (5-FU)-treated patients. The healing effects of rebamipide, a therapeutic agent for stomach ulcer, on areas of injury due to acetic acid-induced oral stomatitis were examined in 5-FU-tunreated and -treated Golden Syrian hamsters. [Methods] The oral stomatitis model was prepared by anesthetizing male Golden Syrian hamsters i.p. with 30 mg/kg pentobarbital. The center of the cheek pouch was then exteriorized and sandwiched between ring forceps 5 mm in inside diameter, followed by submucosal injection of 25 µL of 10% acetic acid solution through the ring forceps. [Results] Application of 3.0 mg/mL rebamipide solution significantly reduced the areas of injury acetic acid-induced oral stomatitis in 5-FU-untreated animals. The application of 4.0 mg/mL rebamipide suspensions in sodium carboxymethylcellulose solutions did not reduce the injured oral areas of acetic acid-induced oral stomatitis. The p.o. administration of 3.0 mg/mL rebamipide solutions did not reduce the injured oral areas. The acetic acid-induced oral stomatitis of 5-FU-treated animals showed significantly larger injured areas than those of 5-FU-untreated animals. The application of 3.0 mg/mL rebamipide solution significantly reduced the injured areas of acetic acid-induced oral stomatitis in 5-FU-treated animals. [Conclusion] These results suggested that the application of rebamipide reduced the injured areas of acetic acid-induced oral stomatitis that developed under 5-FU-untreated and -treated conditions.