To decipher the mechanism of Gehua Jiecheng Decoction in the treatment of chronic alcoholism via COX-2 pathway.Methods:Sixty C57BL/6J mice were randomly assigned into five groups:a normal group,a model group,and low-,medium-,and high-dose Gehua Jiecheng Decoction groups.The COX-2 protein level,delta-opioid receptor(DOR) mRNA level,β-endorphin,cystathionine-beta-synthase(CBS) activity,and H2S level were determined by histological examination,Western blotting,and chemical colorimetry.The alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase(ALDH) activities and the antioxidant indexes including glutathione(GSH),glutathione S-transferase(GST),and total antioxidant capacity(T-AOC) in the liver tissue were compared between groups.Results:The COX-2 protein level,DOR mRNA level,β-endorphin level,CBS activity,and H2S level were lower in the low-dose Gehua Jiecheng Decoction group than in the model group(P<0.05) and lower in the high-dose Gehua Jiecheng Decoction group than in the medium-dose Gehua Jiecheng Decoction group(P<0.05).The activities of ADH and ALDH were higher in the low-dose Gehua Jiecheng Decoction group than in the model group(P<0.05),and the ADH activity in the high-dose Gehua Jiecheng Decoction group was lower than that in the medium-dose Gehua Jiejiu Decoction group(P<0.05).The GSH,GST,and T-AOC levels were higher in the low-dose Gehua Jiecheng Decoction group than in the model group(P<0.05) and higher in the high-dose Gehua Jiecheng Decoction group than in the medium-dose Gehua Jiecheng Decoction group(P<0.05).Conclusion:Gehua Jiecheng Decoction can inhibit COX-2 pathway,decrease DOR mRNA level,β-endorphin level,CBS activity,and H2S level in brain tissue,increase the activities of ADH and ALDH in the liver tissue,and alleviate the oxidative stress in the mice with chronic alcoholism.