The hepatoprotective effect of the ethanol extract of Picrorrhiza kurroa rhizomes and roots (PK) on liver mitochondrial antioxidant defense system in isoniazid and rifampicin-induced hepatitis in rats was investigated. In liver mitochondria of antitubercular drugs administered rats, a significant elevation in the level of lipid peroxidation with concomitant decline in the level of reduced glutathione and in the activities of antioxidant enzymes was observed. Co-administration of PK (50 mg/kg/day for 45 days) significantly prevented these antitubercular drugs-induced alterations and maintained the rats at near normal status.