Introduction: Human subjects can not always used as models for studying disease by researchers because of the potential risks for human health, and in addition, control of interfering factors is not easy in these subjects. Animal biology, physiology, anatomy, biochemistry, pharmacology, and genetics are very similar to humans. Animals are suitable models for research, as their functional body system is similar to humans and is easily manipulated. Most of our current knowledge in medical sciences is obtained from animal studies, among which, rats and mice are mostly used for the their shorter lifespans, which creates the possibility of producing many generations and studying total lifespan. The thyroid plays pivotal role in the body and is vital for normal function of almost all tissues throughout life. Decreased secretion of thyroid hormones from the thyroid gland (hypothyroidism) is a prevalent disorder and as a result animal models of hypothyroidism are often very important for research purposes. Thyroidectomy, genetic manipulation, and using anti-thyroid drugs are the most important ways to induce hypothyroidism in animals. The aim of this study was to review and evaluate different models for induction of hypothyroidism in rat, and in addition to compare the characteristics of rat and human thyroid glands. Conclusions: Anti-thyroid drugs could be used as cheap, available, and simple methods for inducing hypo­thyroidism, although they may also affect the function of other organs.