Objective: To evaluate hepatic injury induced by antituberculosis drugs (ATDs) when administered orally for 2, 4, 6 and 8 weeks and the therapeutic potential of propolis (bee hive product) against ATDs induced hepatic injury. Methods: The ATDs were administered for 8 weeks as well as propolis extract at three different doses (100, 200, 400 mg/kg) conjointly for 8 weeks in rats. Silymarin (50 mg/kg) was given as positive control. Animals were euthanized after 8 weeks; blood and liver samples were collected to perform various biochemicals, serological and histopathological and ultramorphological studies. Results: Significant increase (P < 0.05) in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglyceride and cholesterol along with reduction in glucose and albumin level were noted after ATDs induced hepatic injury. Significant increase (P < 0.05) in lipid peroxidation, triglyceride, cholesterol and CYP2E1 activity; decline in reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glucose-6-phosphatase dehydrogenase activity were observed after ATDs intoxication. Due to presence of a wide range of flavonoids and polyphenols in propolis extract, its administration reduced hepatic injury and maintained biochemical indices towards control. Histopathological and electron microscopic observations indicated hepatoprotective potential of propolis at cellular level whereas, TNF- α, IL-6 and IGF-1 confirmed therapeutic potential of propolis at molecular level. Conclusions: It can be concluded that propolis possess hepatoprotective potential against ATDs induced hepatic injury that may prove itself as a clinically useful natural product in management of drug induced liver injury.