Objective To observe the protective effects of quercetin on esophageal mucosa in chronic mixed reflux esophagitis (RE) rats and the effect of quercetin on nuclear factor (NF)-κB/interleukin (IL)-6 signaling pathway.Methods Mixed RE model was successfully induced by cardia ligation and esophagoduodenostomy.48 healthy male Sprague-Dawley rats were equally divided into the following 6 groups using random number table method:normal control group,sham-operation group,model control group,omeprazole group,low-dose quercetin group,and high-dose quercetin group.The 6 groups were treated with peritoneal injection of 2 ml normal saline (normal control,sham-operation,model control groups),20 mg/kg omeprazole,100 mg/kg quercetin (low-dose) and 200 mg/kg quercetin (high-dose) once daily,respectively.The rats were sacrificed after 6 weeks of intervention.The microscopic pathological changes of esophageal mucosa were scored.NF-κB p65 and IL-6 protein levels in esophageal mucosa and serum were assessed using immunohistochemistry and enzyme-linked immunosorbent assay,respectively.Results In normal control group,shamoperation group,model control group,omeprazole group,low-dose quercetin group and high-dose quercetin group,the pathological scores of esophageal mucosa were 0.250 ± 0.463,0.250 ± 0.463,2.625 ± 0.518,1.500 ±0.535,1.250 ±0.463,and 1.375 ±0.518; the NF-κB p65 protein scores in esophageal mucosa were 0.500±0.535,0.625 ±0.518,3.500 ±0.535,1.875 ±0.649,1.750 ±0.707,and 2.000 ±0.535; the IL-6 protein scores in esophageal mucosa were 1.125 ± 0.641,1.125 ± 0.835,5.375 ± 0.518,2.375 ± 0.518,2.000 ±0.535,and 2.250 ±0.463; the serum NF-κB p65 protein levels were (68.618 ± 18.500),(77.824 ± 22.228),(184.882 ± 49.165),(106.693 ± 45.312),(76.215 ± 16.588),and (108.207 ± 42.107) pg/ml; the serum IL-6 protein levels were (24.826 ±4.008),(23.599 ±4.351),(51.378 ± 9.697),(32.370 ± 11.657),(23.085 ± 4.660),and (26.243 ± 4.955) pg/ml.In terms of the 5 indicators,there were no statistically significant differences between the normal control group and the sham-operation group (P =1.000,P =0.642,P =1.000,P =0.518,P =0.673) ; the results in the normal control,shamoperation,omeprazole,low-dose quercetin,and high-dose quercetin groups were significantly different from those in the model control group (P < 0.001,P < 0.001,P < 0.001,P =0.002,P =0.001 ; P < 0.001,P < 0.001,P<0.001,P=0.004,P=0.002; P=0.001,P<0.001,P<0.001,P=0.025,P=0.023; all P <0.001 ; P <0.001,P <0.001,P <0.001,P =0.023,P <0.001) ; there were no statistically significant differences between low-dose quercetin group and omeprazole group,nor between high-dose quercetin group and omeprazole group (P=0.334,P=0.717,P=0.176,P=0.121,P =0.074; P =0.642,P=0.678,P=0.619,P =0.949,P =0.225); there were no statistically significant differences between low-dose quercetin group and high-dose quercetin group (P =0.619,P =0.438,P =0.334,P =0.086,P =0.243).The microscopic pathological score of esophageal mucosa was positively correlated with NF-κB p65 and IL-6 protein scores in esophageal mucosa (r =0.803,P < 0.001 ; r =0.758,P < 0.001),also positively correlated with serum NF-κB p65 and IL-6 protein levels (r=0.486,P=0.004; r=0.544,P=0.001).Conclusions The expression levels of NF-κB p65 and IL-6 protein in esophageal mucosa and serum increase with the severity of esophageal mucosal injury.Quercetin can reduce the severity of esophageal mucosal injury in RE,possibly through down-regulating NF-κB and IL-6 expression and mitigatng esophageal inflammatory status.