Objective: In this study anti-tubercular (Anti-TB) drugs (isoniazid [INH] and rifampicin [RMP]) induced liver toxicity has been studied for the hepatoprotective effect of hydroethanolic extract of Calotropis procera (CP) fl owers in rats. Materials and Methods: Animals were divided into four groups, group A was given normal saline (1 ml/kg), group B received INH (50 mg/kg) and RMP (100 mg/kg) group C received INH (50 mg/kg), RMP (100 mg/kg) and CP (150 mg/kg) orally for 14 days. Results: Biochemical markers of liver toxicity such as aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin and tissue histology were done inall groups. Anti-TB drugs (INH 50 mg/kg and RMP 100 mg/kg) have enhanced the ALT, AST, ALP, bilirubin and histological changes in liver, whereas co-administration of anti-TB drugs with CP has reduced these levels within the normal range. Conclusion: Findings of this study showed the hepatoprotective effect of CP against INH and RMP administration to reduce the liver damage for chronic treatment.