[Background] We studied whether rebamipide would exert healing effects in an acetic acid-induced model of oral stomatitis in animals either untreated or pretreated with 5-FU. [Methods] The oral stomatitis model was prepared by anesthetizing male Golden Syrian hamsters. 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] In animals un-pretreated with 5-FU, rebamipide at 3 mg/mL was shown to significantly inhibit acetic acid-induced oral stomatitis in comparison with animals that did not receive rebamipide. The area of oral injury in 5-FU-pretreated animals was significantly greater than that in animals not pretreated with 5-FU. The recovery time in 5-FU-pretreated group was longer than that in the 5-FU-un-pretreated group. In 5-FU-pretreated animals, the area of oral injury was significantly reduced in those that received 3 mg/mL rebamipide in comparison with those that did not receive rebamipide. [Conclusion] The present findings suggest that rebamipide has healing effects on acetic acid-induced oral stomatitis in animals both pretreated and un-pretreated with 5-FU.