Drug-induced liver injury (DILI) is the major health problem that resulted from uses of many drugs especially from serious adverse effect of antituberculosis (ATT) drugs. forty eight rats (200-250g) were allocated into six groups (8 rats in each group), and treated as follow: group I: received normal saline orally; group II: received INH/RFP (50 mg/Kg/day of each) for 28 days orally; group III: received Silymarin (50 mg/kg/day) + INH/RFP for 28 days orally; group IV: received SNME(250 mg/Kg/day) + INH/RFP for 28 days orally; group V: received SNME (500 mg/Kg/day) + INH/RFP for 28 days orally; group VI, received SNME (1000 mg/Kg/day) + INH/RFP for 28 days orally. Co-administration of herbal plant (SNME) with INH/RFP reduced elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and (bilirubin total &direct) levels but also decreased the elevated malondialdehyde (MDA) & tumor necrosis factor-α (TNF-α) contents in liver homogenate. Moreover, co-administration of herbal plant (SNME) with INH/RFP increased glutathione peroxidase (GPX) & adiponectin activity. Solanum nigrum administration to rats, in present study, led to a remarkable alteration of histological changes observed in INH/RFP group. It is concluded that Solanum nigrum might be considered as adjuvant drug in treatment of liver disorder and/or as hepatoprotective therapy with anti-tubercular drugs.