Numerous studies have reported that human umbilical cord mesenchymal stem cell (hUCMSC) therapy can rescue the structure and function of injured tissues. The aims of this study were to explore the protective role of hUCMSC transplantation in a model of accelerated ovarian aging and to compare 2 methods of transplanting hUCMSCs, i.e. i) via intravenous injection (IV) and ii) in situ ovarian micro injection (MI). Female mice were subjected to superovulation and ozone inhalation to create a model of accelerated ovarian aging with a decline in both the quantity and quality of oocytes. Cells were transplanted via IV or MI, and ovaries were removed after 2 weeks or 1 month of treatment. Ovarian reserve and function were evaluated based on the follicle counts, hormone levels, the estrous cycle, and reproductive performance. Cell tracking, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), real-time polymerase chain reaction (PCR), and Western blot analysis were used to assess the inner mechanisms of injury and repair. Results indicated that ovarian function increased significantly after treatment with hUCMSCs. Immunofluorescence revealed reduced TUNEL staining and a decreased percentage of apoptotic cells. A higher level of expression of anti-apoptotic and antioxidant enzymes was noted in the ovaries of groups treated with hUCMSCs. These parameters were enhanced more when mice were treated with hUCMSCs for 1 month than when they treated with hUCMSCs for 2 weeks. IV was better able to restore ovarian function than MI. These results suggest that both methods of transplantation may improve ovarian function and that IV transplantation of hUCMSCs can significantly improve ovarian function and structural parameters more than MI transplantation of hUCMSCs can.