Isoniazid (INH) continues to be a highly effective drug in the chemoprophylaxis and chemotherapy of both active and latent forms of M. tuberculosis infections and is the most widely used of all anti-tuberculous drugs. This study was carried out to investigate the morphological and ultrastructural alterations resulting from isoniazid administration in the liver of adult albino rat and the possible protective role of silymarin against these hepatic changes. INH induced hepatotoxic effect mainly in the form of disruption of the architecture, congestion of veins and sinusoids and degenerative changes in the hepatocytes. These adverse effects were alleviated when silymarin was concomitantly administered but the hepatoprotective role was only partial when silymarin was given two weeks after INH treatment.