Study aimed to evaluate the diagnostic value of hepatocyte-derived microRNAs and their genes, MDA, GSH and GPX in experimental rat model of liver damage induced by isoniazid. In this study, 72 adult male rats (130-150 gm) were divided into six groups and given treatments for 21 days: control group:(1 ml saline /Kgb.wt/day I/P).INH group: 100 mgINH/kgb.wt/dayI/P. INH + Rutingroup: 100 mg INH/kg b.wt/day I/Pwith 200 mgrutin/kg b.wtorally. INH + NAC group: 100 mg INH /kg b.wt/day I/Pwith 300 mgNAC/kg/day b.wt orally. Rutingroup: 200 mgrutin/kg/day orally.NAC group: 300 mg NAC /kg b.wt orally. Tissue samples were obtained after 14 and 21 days foranti-oxidants as well as miRNAs 122 and 125b, CyclinG and STAT3 detection. Isoniazid injection into male rats induced a significant upregulation of CG1and STAT3 expression levelconcomitant with a downregulation of miRNA122 and miRNA125b.Meanwhile, ratstreated with rutin or NAC combined with INH developed a downregulation of CG1gene and STAT3 expression levelwithupregulation of miRNA122 and miRNA125b. INH induced a significant increase in MDA levelwith a significant decrease in GSH concentration and GPx activity. While INHinjection with rutin or NAC treatment induced asignificant decrease in MDA level with a significant increase in GSH concentration and GPx activity.Taken together these findings suggest that hepatocyte-derived microRNAs 122 and 125bcould beused as early sensitive biomarkers for hepatotoxicity inducedduring isoniazid treatment.