Cell-based therapies with certain cell types are touted as novel and hopeful therapeutic intervention in the clinical setting. Here, we aimed to assess the regenerative potential of c-Kit cells in the rejuvenation of ovarian tissue and fertility rate in rat model of premature ovarian failure (POF). Rats were treated with 160 mg/kg/BW of 4-vinylcyclohexene dioxide for 15 days. Freshly enriched rat bone marrow-derived c-Kit (MACS) and c-Kit cells (4×10 cells/10 µL) were transplanted into the ovaries of treatment and control animals. Prior to transplantation as well as 2, 4, 6, and 8 weeks post-transplantation, randomly-selected rats were euthanized and ovarian tissues were subjected to pathophysiological examinations and real-time PCR analyses. POF status was confirmed by the presence of pathological features and a decreased number of immature and mature follicles compared with the control group (< 0.05). Histological examination revealed a substantial reduction of atretic follicles in POF rats receiving c-Kit cells in comparison with POF rats that did not receive these cells (< 0.05). Compared with the control samples, angiogenesis-related genes, and , showed increased and decreased expressions in POF ovaries, respectively (< 0.05). c-Kit cells had potential to restore angiogenesis in the ovarian tissue within normal ranges. Systemic levels of FSH did not significantly change in pre- or post-transplantation time points for any group (> 0.05). Notable reduction of collagen deposition was found in c-Kit-treated rats. Transplantation of c-Kit cells also restored the reduced fertility rate (< 0.05). The administration of c-Kit cells can modulate angiogenesis and pathological changes, leading to the rejuvenation of ovarian function of a rat model of premature menopause.