Objective: Reflux esophagitis animal models represent an important component in the preclinical study of digestive system drugs, and the aim of this study was to determine the best modeling method. Methods: Female Wistar rats were used to establish reflux esophagitis models by employing the following methods: improved chemical burn, external pyloric clamp plus anterior gastric ligation, cardiomyotomy plus semipyloric ligation, cardiomyotomy plus internal pyloric ligation, cardiomyotomy plus external pyloric ligation, and cardioplasty plus pyloric ligation plus gastrojejunal Roux-en-Y anastomosis. The body weight, lower esophageal pH and esophageal mucosal injury of the rats were observed. Results: The model formation rate was 83% based on cardiomyotomy plus external pyloric ligation. On the 3rd day after the operation, lower esophageal mucosa congestion occurred, and the model was successfully established. On the 7th day, mucosal hyperemia and erosion were observed in the most serious lesions, indicating optimal model conditions. On the 14th day, the lower esophageal mucosa remained congested, suggesting that the model was useful from the 3rd to the 14th day. The method caused less trauma to the animals. The ligation diameter was uniform, and the model was more stable. Conclusion: Cardiomyotomy plus external pyloric ligation is the best method.