Here, we aimed to use TMT based quantitative proteomics approach to investigate rodent thyroid toxicity. For this purpose, male Wistar rats have been exposed to a direct (6-propyl-2-thiouracil, PTU) and an indirect (phenytoin) thyroid toxicant, respectively. Thereby, two doses (high, low) and three treatment time points (short, long, and long+recovery) were investigated, allowing insights into the mode of actions during thyroid toxicity. Proteomics were applied to liver and thyroid tissues.