Objective:To observe the protective effects of Hezhong Jianpi Decoction on the esophageal mucosal injury in rats with mixed reflux esophagitis and its effects on nuclear transcription factor-кB (NF-кB) signaling pathway, which mediated the inflammatory response. MethodsSixty healthy male SD rats of SPF grade were randomly divided into the normal group, sham operation group, model group, Hezhong Jianpi Decoction group and omeprazole group according to the random number table, 12 rats in each group. The rat model of mixed reflux esophagitis was established. 3 days after modeling, the rats were treated the corresponding drug by intragastric administration for 14 days. The histopathological changes of esophageal tissues were observed and scored. Meanwhile, the serum levels of interleukin-6 (IL-6), IL-8 and NF-кB p65 were detected.  Results:The naked eye and pathological scores of esophageal mucosal and the serum expressions of NF-кB p65, IL-6, and IL-8 in the model group were significantly higher than those in the normal group, sham operation group, Hezhong Jianpi Decoction group and omeprazole group (P<0.05). There were no statistically significant differences on the naked eye and pathological scores of esophageal mucosal between the Hezhong Jianpi Decoction group and the omeprazole group (P>0.05). The serum expressions of NF-кB p65, IL-6, and IL-8 in the Hezhong Jianpi Decoction group were higher than those in the omeprazole group (P<0.05).  Conclusion:Hezhong Jianpi Decoction can reduce the pathological damage degree of esophageal mucosa in rats with reflux esophagitis. Its mechanism may be related to down-regulating the serum expression levels of proinflammatory cytokines IL-6, IL-8 and NF-кB p65 in model rats, and thus relieving the esophageal inflammatory response to exert anti-inflammatory effects.