We investigated the pathogenesis of skin lesions due to hypothyroidism and hyperthyroidism in rats. We used 30 rats allocated into hypothyroidism, hyperthyroidism and control groups. Blood samples were evaluated for levels of thyroid stimulating hormone (TSH), tri-iodothyronine (T3) and thyroxine (T4). Skin samples were examined for melan-A, lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1), cluster of differentiation 31 (CD31), protein gene product 9.5 (PGP9.5), calretinin, chromogranin, synaptophysin and pancytokeratin. Histopathological examination of the skin sections revealed thickened epidermis in the hyperthyroidism group due to an increased number of cells, and a decreased number of hair follicles and epithelial cell rows in the epidermis with an increased number of fat cells in the dermis of the rats in the hypothyroidism group. No significant difference was observed in the immunoreactions of pancytokeratin, PGP9.5, CD31 and synaptophysin among the groups. The hyperthyroidism and hypothyroidism groups exhibited a marked increase in melan-A immunoreaction. Expression of LYVE-1, chromogranin and calretinin was increased in the hyperthyroidism group and decreased in the hypothyroidism group. We found that melan-A, LYVE-1, chromogenin and calretinin play an important role in the pathogenesis of skin lesions caused by thyroid disorders.