Objective To observe the effectiveness of Shiguanning (SGN) decoction, a traditional Chinese medicine (TCM) formula, on reflux esophagitis (RE). Methods A total of 60 male SD rats were randomly divided into sham operation group (sham group), model group (M group), low- and high-dose SGN groups (1 and 2 g/ml SGN, L and H groups), and the positive control group (esomeprazole magnesium enteric-coated tablet 0.24 mg/ml, W group), each with 12 rats. The rat model of RE was established with pyloric ligation and lower esophageal sphincter incision operation. The sham group only underwent open and closed abdominal surgery. Then the histopathological score, plasma content of motilin (MTL) and mRNA levels of interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) of esophageal tissues were compared among the groups. SPSS statistics 22.0 was used to perform the statistical analysis. Chi-square test or rank sum test was employed for intergroup comparison depending on different data types. Results The M group had the highest histopathological score of esophageal mucosa, lowest plasma content of MTL, and highest mRNA levels of IL-17 and TNF-α when compared with the other 4 groups (all P<0.05). Conclusion SGN can elevate the plasma content of MTL, thereby increasing the pressure of the lower esophageal sphincter; inhibit the mRNA expression of IL-17 and TNF-α in esophageal tissue, thus alleviating the inflammatory response. SGN have therapeutic effects on RE.