〔Abstract〕 Objective To analyze the changes of gut microbiota during isoniazid(INH)-induced anti-tuberculosis drug-induced liver injury(ADLI) in rats using 16 S rDNA sequencing technology. Methods 24 male SD rats were randomly divided into control group(D0 group),INH gavage 10 d group(H10 group),INH gavage 28 d group(H28 group).After continuous gavage for 0 d, 10 d and 28 d, fresh rat feces were collected for 16 S rDNA sequencing to analyze the structure and composition of the intestinal flora. And liver tissues were taken for HE staining to observe the pathological changes of rat liver tissues. Results Compared with D0 group, the α diversity of H10 group and H28 group did not change(allP>0.05),the β diversity changed(allP<0.05),and the abundance of Verrucomicrobia at the phylum level showed a decreasing trend, while the abundance of Tenericutes showed an increasing trend(allP<0.05),and the abundances of Lactobacillus, Romboutsia, and Akkermansia at the genus level showed a decreasing trend, while the abundance of Ruminococcaceae_UCG-005,Dubosiella, norank_f__norank_o__Mollicutes_RF39,unclassified_f__Ruminococcaceae, Roseburia and Blautia showed an increasing trend(allP<0.05). Conclusion The structure and species composition of intestinal microflora changed in rats with ADLI induced by INH.