THIS work aims at detecting the disturbances in thyroid hormone metabolism in male rats exposed to liver injury by γ- radiation and/or carbon tetrachloride (CCl4), in addition to investigating the modulatory role of N-acetyl cysteine (NAC) and sodium selenite (Se) supplementation. Subcutaneous injection of CCl4 twice a week for 8 weeks and/or whole-body irradiation (6 Gy, single dose) one day after the last dose of CCl4 induced hepatotoxicity as manifested by elevation of serum alanine aminotransferase and gamma-glutamyl transferase and oxidative stress in liver tissue. Moreover, significant increases were recorded in pro-inflammatory markers: nuclear factor kappa B and interleukin- 1beta levels. This was also accompanied by a significant decrease in the activity of type 1 iodothyronine deiodinase in the hepatic tissue and triiodothyronine and thyroxin levels in serum, while thyroid-stimulating hormone showed a non-significant increase. Histological examination of liver sections showed marked alterations. However, oral supplementation of NAC and Se for 2 weeks after exposure to CCl4 and/or γ- radiation attenuated the changes induced by these toxins. In conclusion, supplementation of NAC & Se may be useful to attenuate thyroid hormone metabolic disturbances associated with liver injury induced by chemical and physical environmental toxins.