Objective To investigate the effect of Ilex pubescens extract on the wound healing effect of mice with radiation oral mucositis and to explore its possible mechanism. Methods Male C3H mice with 8 weeks old were selected to reproduce the model of radiation oral mucositis（RTOM）in mice by X-ray irradiation of the oral and tongue parts. They were randomly divided into model group,positive control and experimental groups. HE staining was used to observe the recovery of mucosal lesions and the density of fibroblasts. The expression of IL-6 and TNF-α protein was detected by immunohistochemistry. Results The mouse RTOM model was successfully replicated. After 7 days,the model group mice showed grade III oral ulcer,thinning of the oral mucosal epithelial layer,slight disorder of keratinized epithelial structure,dilation of capillaries,and visible infiltration of inflammatory cells;The mice in the cell growth factor group exhibited grade II oral ulcer,slightly increased thickness of buccal mucosal epithelium compared to the normal group,and normal keratinized epithelial structure;After 7 days of treatment,the mice in the Ilex exract group showed grade I oral ulcer,increased keratinization of the buccal mucosa,and normal keratinized epithelial structure. Immunohistochemical and Western blot results showed that the expression of TNF - and IL-6 in the cheek mucosa of mice in the cell growth factor group and Ilex exract group was significantly lower than that in the model group. The expression of TNF - and IL-6 in the cheek mucosa of mice in the Ilex exract group was significantly lower than that in the cell growth factor group. The positive rates of TNF - and IL-6 expression in the cell growth factor group and Ilex exract group were significantly lower than those in the model group. The positive rates of TNF - and IL-6 expression in the Ilex exract group were significantly lower than those in the cell growth factor group. Conclusion Extracts of Ilex have a repairing effect on ulcer wounds in mice with RTOM.