Objective To investigate the effect of two indomethacin preparations on the healing process of oral ulcers.Methods After the right cheek of rats were burned with nails,they were divided into indomethacin gel to medicine group (YN), compound benzocaine gel positive control group (NP), indomethacin spray to medicine group (YP), stomatitis spray, normal control group (PP), positive control group (N) and the negative control group (M). The reepithelialization of ulcer surface and granulation tissue formation was evaluated after HE staining with histological quantitative standard evaluation. The level of nitric oxide (NO) and nitric oxide synthase (NOS) in ulcer tissues was detected by colorimetry. The expressions of epidermal growth factor (EGF), as well as its receptor (EGFR) and vascular endothelial cell growth factor (VEGF) in rat ulcer tissues, were detected by immunohistochemistry.Results The ulcer area of the YP, YN, NP, and PP groups was smaller than that of the M group. The quantitative histological evaluation showed that the scores of the YP, YN, NP, and PP groups were higher than that of the M group (P<0.05). After administration, the level of NO and NOS in the YP group were significantly lower than that of M group (P<0.05). The EGF expression of YP, YN, NP, and PP groups was higher than that of the M and N groups (P<0.05). EGFR was expressed in the epithelium from the cytoplasm to the membrane, and the expression level in the YP, YN, NP, and PP was significantly higher than that of the N group (P<0.05). The VEGF expression of YP, YN, NP, and PP groups was lower than that of the M group (P<0.05).Conclusion Both two indomethacin preparations can reduce the inflammatory response and promote the healing of oral ulcers in rats.