We analyzed whole cell protein content of rat liver following T3 administration. Fourteen differentially expressed proteins were unambiguously identified and were involved in substrates and lipid metabolism, energy metabolism, detoxification of cytotoxic products, calcium homeostasis, amino acid catabolism, and the urea cycle. This study represents the first systematic identification of T3-induced changes in liver protein expression profile and provides novel information at the molecular, cellular, and tissue level of T3 action.