〔Abstract〕 Objective To investigate the regulatory mechanism of zeste gene enhancer human homologue 2(EZH2) on nrf2-are REDOX pathway in drosophila melanogaster in anti-tuberculous drug-induced liver injury(ADLI).Methods 32 kunming mice were randomly divided into four groups: blank control group,model group,experimental group and negative control group.The levels of ALT and AST in serum liver function indexes were detected by microporous plate method.Histopathological changes of liver were observed by HE staining.MRNA and protein levels of EZH2,nuclear factor e2-related factor 2(Nrf2),NADPH quinone oxidoreductase 1(NQO1) and heme oxygenase 1(HO-1) were detected by real-time quantitative fluorescence PCR,ELISA and Western blot,respectively.Results The serum ALT and AST levels of mice in the model group were higher than those in the blank control group(all P<0.05),while those in the experimental group were lower than those in the model group(all P<0.05).Compared with the blank control group,the liver histopathological results of mice in the model group showed obvious injury,while the liver injury of mice in the experimental group was alleviated.Compared with the blank control group,the mRNA and protein levels of EZH2 decreased in the model group( P<0. 05),and further decreased in the experimental group( P<0. 05). Compared with the blank control group,the mRNA and protein levels of Nrf2,NQO1 and HO-1 increased in the model group( P<0. 05),and further increased in the experimental group( P<0. 05). Chip results showed that the level of H3 K27 me3 in the model group was lower than that in the blank control group( P<0. 05),and further decreased in the experimental group( P<0. 05). Conclusion The down-regulation of EZH2 expression in ADLI and the inhibition of EZH2 expression can alleviate the degree of liver injury. The effect of EZH2 on ADLI may be realized through the modification of H3 K27 me3 in the Nrf2 promoter region,and then through the regulation of Nrf2-ARE antioxidant stress pathway.