The effect of isoniazid and rifampicin on metabolism dependent hepatotoxicity of methimazole (MMI) was studied in BALB/c mice. Hepatic damage was induced by single intraperitoneal dose of MMI (1000mg/kg). Pretreatment with isoniazid and rifampicin was carried out in separate groups for ten days and six days respectively prior to administration of methimazole. The extent of liver injury was determined by measuring alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) along with histopathological analysis of liver samples. The elevation of liver enzyme levels caused by MMI was augmented by rifampicin however; isoniazid exhibited a protective role by preventing MMI induced escalation in serum ALT, AST and ALP. The biochemical findings were also reflected in histological examination. These findings suggest that activity of microsomal enzymes can influence the hepatotoxic potential of MMI