OBJECTIVE To investigate the effect of saikosaponin A (SA) on inflammatory injury in rats with reflux esophagitis (RE) by regulating the interleukin (IL)-6/tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. METHODS SD rats were randomly divided into RE group, normal group, SA low-dose group (gavage of 12.5 mg·kg^-1 SA), SA high-dose group (gavage of 50 mg·kg^-1 SA), omeprazole group (gavage of 2 mg·kg^-1 omeprazole), SA high-dose+IL-6 activator recombinant rat IL-6 protein (rRIL-6) group (gavage of 50 mg·kg^-1 SA+intraperitoneal injection of 0.05 mg·kg^-1 rRIL-6), with 12 rats in each group. Except for the normal group, rats in all other groups were required to undergo RE model construction through fore-stomach ligation combined with partial ligation of the external pylorus. After successful modeling, the drug was administered once a day for 2 weeks. The damage rate of esophageal mucosa was detected. Hematoxylin-eosin staining(HE) was applied to detect pathological changes in esophageal tissue. Enzyme-linked immunosorbent assay (ELISA) was applied to detect levels of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and IL-8 in esophageal tissue. Terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was applied to detect cell apoptosis in esophageal tissue. Immunohistochemical staining was applied to detect the expression of claudin-5 in esophageal tissue. Western blot was applied to detect IL-6, p-JAK2, and p-STAT3 proteins in esophageal tissue. RESULTS Compared with the normal group, the esophageal tissue compactness of rats in the RE group decreased, and there was a large amount of inflammatory cell infiltration, the incidence of esophageal mucosal injury, levels of TNF-α, COX-2, IL-8 in esophageal tissue, apoptosis rate, and the expression of IL-6, p-JAK2, and p-STAT3 proteins increased, while the average optical density of claudin-5 in esophageal tissue decreased (P<0.05). Compared with the RE group, the pathological damage to the esophageal tissue of rats in the SA low-dose group, SA high-dose group, and omeprazole group was reduced, the incidence of esophageal mucosal injury, levels of TNF-α, COX-2, IL-8 in esophageal tissue, apoptosis rate, and the expression of IL-6, p-JAK2, and p-STAT3 proteins decreased, while the average optical density of claudin-5 in esophageal tissue increased (P<0.05). Compared with the SA high-dose group, the SA high-dose+rRIL-6 group had severe pathological damage to the esophageal tissue, the incidence of esophageal mucosal injury, levels of TNF-α, COX-2, IL-8 in esophageal tissue, apoptosis rate, and the expression of IL-6, p-JAK2, and p-STAT3 proteins increased, while the average optical density of claudin-5 in esophageal tissue decreased (P<0.05). CONCLUSION SA may improve inflammatory injury in RE rats by inhibiting the IL-6/JAK2/STAT3 signaling pathway.