Introduction: The adverse effects of hyperthyroidism are related to its duration and the level of thyroid hormone excess. They include cardiac arrhythmias, atrial fibrillation, and even congestive heart failure, renal disorders, and pancreatic injury. Aim of work: To assess the harmful effect of hyperthyroidism on the structure of the pancreas of the adult female albino rats and the therapeutic role of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) as a new strategy in ameliorating pancreatic injury. Material and Methods: Forty adult virgin female albino rats were assigned to control and treated groups. The treated one was subdivided into hyperthyroid and hyperthyroid + hUCB-MSCs subgroups. Serological analysis was carried out to assess thyroid and pancreatic functions by measuring thyroid-stimulating hormone (TSH), glucose, insulin, amylase levels. Also, anti-oxidant marker as the product of lipid peroxidation malondialdehyde (MDA), and superoxide dismutase (SOD) activity were measured. Pancreatic samples were processed for light microscopic examination. Immunohistochemical examination for insulin protein, caspase-3, PCNA, and CD105 was carried out. Results: Hyperthyroidism produced biochemical and histopathological alterations in the pancreatic tissue. There was a significant decrease in TSH, serum insulin, serum amylase levels, and SOD enzymes activity but a significant increase in blood glucose and in MDA level in the hyperthyroid group. The acinar cells appeared with vacuolated cytoplasm and dark nuclei. Inflammatory cells, wide septa, and many collagen fibers were noticed. Cytoplasmic immunoreactivity of insulin in beta-cells was reduced; the cytoplasmic reaction of caspase3 was strong in most of the islets and some acini. There were few PCNA positive immunoreactive nuclei in some islet and acinar cells. After hUCB-MSCs injection, the serological and oxidative markers were significantly ameliorated resulting in a nearly normal structure of the pancreas. Conclusion: Pancreatic tissues were seriously affected by hyperthyroidism with subsequent disturbance in the biochemical markers. Human UCB-MSCs nearly normalized these biochemical and histological changes.