Hypoparathyroidism (hypo-PT) is a disease, caused by the lack of parathormone (PTH) and accompanied by a decrease in the calcium and an increase in the phosphate levels in serum. Lifelong use of high doses of oral Ca and vitamin D supplements are mandatory in the conventional treatment of chronic hypo-PT. Although the conventional treatment is symptomatic but not curative, it may cause very serious side effects in long-term use. Therefore, the necessity of developing new alternative therapies for hypo-PT is clearly seen. Gene therapy is a therapy method that can be preferred especially for the diseases that do not have a curative or effective treatment. Both its reliability and effectiveness have been increased in recent years due to the renewed gene transfer vector designs. Therefore it's aimed to show that it is possible to create an ex vivo gene therapy method for hypo-PT treatment on rats Our study is both the "first ex vivo gene therapy using autologous primary cells" and the "first study using lentiviral vectors for gene delivery" in the treatment of hypo-PT. Even if, in vivo gene therapy studies for hypo-PT have been performed before, "ex vivo method" which is preferred in our study, is more safer and manageable than "in vivo method". In our study, it was also aimed to prevent immune rejection by using autologous primary cells. In our thesis, seperate skin biopsies were excised from experimental animals and seperate autologous cell cultures were created for each animal. At the same time, lentiviral vector particles which are carrying "hPTH therapeutic gene" was constructed and then the autologous cells were transduced by lentiviral vectors to integrate the therepeutic gene hPTH into their genomes. Following transduction, high amounts of biologically active hPTH production and secretion from autologous cells was confirmed by both flourescent microscope images and biochemical tests. Thereafter therapeutic cells were injected subcutaneously into the rat body and hPTH production was confirmed in all experimental animals, demonstrating that "treatment of hypo-PT with ex vivo gene therapy in rats" may be feasible. However, it is observed that the hPTH values measured from the serum of rats after the therapy, remained below the physiological PTH reference range, it is estimated that the reason for this is that only a small amount of the therapeutic cells could engraft in the body after the injection, and the vast majority of them are removed due to the fact that they couldn't engraft into the body. As a result, due to the inadequate engraftment ratios of therapeutic cells, it is thought that hPTH levels remained below the physiological PTH reference ranges. In our future studies, it is planned to optimize the study protocol and to apply the injection of therapeutic cells with a suitable cellular matrix, thereby increasing the engraftment ratios of therapeutic cells into the rat body and thus the amount of hPTH production.