Background Hypothyroidism is a common endocrine disorder characterized by a deficiency of thyroid hormones less than the normal levels. Recent research studies identified the presence of stem cells that act as a source of tissue regeneration within the thyroid gland. Aim To investigate the role of resident thyroid stem cells on the hypophyseal thyroid axis in experimentally induced hypothyroidism in male rats. Materials and methods A total of 30 healthy male rats were randomly divided into three groups. Group I was the control group). Group II was the hypothyroid group. It received carbimazole in a dose of 0.6 mg/kg dissolved in water to induce hypothyroidism. It was administered via an orogastric tube daily for 3 months. Group III was the withdrawal group. It included hypothyroid animals, as in group II, that were left without treatment for another month and then killed to assess hypothyroidism’s recovery. The thyroid and pituitary glands were extracted from all groups and processed for histological and immunohistochemical analysis. Results The present study revealed that hypothyroidism caused marked histological changes in the pituitary–thyroid axis. Shrunken thyroid follicles with a significant increase in the epithelial height were seen. The colloid decreased in follicles or was completely absent in others. The follicular cells showed vacuolated cytoplasm. A  significant increase in the number of parafollicular cells was observed. Thyrotrophs also appeared vacuolated with an increase in their number. Increase in the apoptotic cells and vascular endothelial growth factor-immunostained cells were observed. The withdrawal group showed moderate improvement in the architecture of the thyroid and pituitary glands. These results were confirmed by the morphometric and thyroid function test analysis. Conclusion The presence of resident thyroid stem cells led to moderate thyroid structure improvement but was not sufficient to restore the normal thyroid function.