Rebamipide is an antiulcer drug that found to be effective in treatment of chemotherapy induced oral mucositis. This study investigates possible role of keratinocyte growth factor (KGF) and interleukin 10 (IL-10) in rebamipide healing activity. Mucositis was induced by single IP injection of 5- fluorouracil  (5-FU) (150 mg/kg).  A subsets of 5-FU treated rats were treated with rebamipide suspension (30 mg/kg/ two times a day). Mucositis was assessed according to WHO grading system. Malondialdhyde (MDA), superoxide dismutase (SOD), expression of IL-10, myeloperoxidase (MPO) and KGF was also assessed. Oral mucositis incidence was decreased in Rebamipide treated rats compared to 5-FU. Rebamipide induced a significant (p≤ 0.001) decrease in oxidative markers induced by 5-FU.  Rebamipide significantly inhibited expression of MPO (p≤ 0.001) as well as upregulated IL-10 (p≤ 0.01) and KGF (p≤ 0.001) compared to 5-FU.  In conclusion, Rebamipide ameliorated 5-FU induced oral mucositis. The healing effect of rebamipide may be due to IL-10 and KGF upregulation.