The anti-tuberculosis drugs Isoniazid (INH) and Rifampicin (RIF) are known to be hepatotoxic agents. Wistar albino rats have been used as a model for INH and RIF induced hepatotoxicity. We have in the present study looked at the chronological progression of liver injury (AST, ALT, ALP), oxidative damage (Super Oxide Dismutase, Catalase, Glutathione peroxidase, Lipid peroxidation) and immune response (IL-6, IL-10 and CD3 levels) to INH and RIF induced liver injury on the 7th, 14th, 21st and 28th days of treatment. Our study has shown that biochemical changes precede changes in the immunological parameters. It is also seen that INH and RIF induce hepatotoxicity at a slower pace than other known liver toxins as seen by its progression. An initial pro-inflammatory response with infiltration of T cells, macrophages and natural killer T cells followed by an anti-inflammatory response as seen by increase in CD3 and IL-10 levels. This has shown that Wistar albino rats provide a robust model for immune changes during INH and RIF induced liver injury.