Asteracantha longifolia Nees. (Family-Acanthaceae) is a wild herb commonly used as aphrodisiac, tonic, sedative and blood diseases etc. The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Asterantha longifolia (AL) plant extract is known to be an effective agent for liver protection and liver regene-ration. The aim of this study was to investigate the protective actions of hydroalcoholic extract of AL against hepatotoxicity caused by different combinations of anti-tuberculosis drugs. Male Sprague-Dawley rats weighing 170–230 g were used to form three study groups, each group consisting of 6 rats.Animals were treated with oral administartion of isoniazid (50 mg/kg) and rifampicin (50 mg/kg). Hepatotoxicity was induced by INH + RIF’s combination. Hepatoprotective effect of AL was investigated by co-administration of AL together with the drugs. Serum biochemical tests for liver functions and histopatho-logical examination of livers were carried out to demonstrate the protection of liver against antituberculosis drugs by silymarin. Treatment of rats with INH+RIF induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline pho-sphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of AL plant extract significantly decreased the biochemical and histological changes induced by the drugs. The active components of AL plant extract had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models.