Exosomes released by bone marrow mesenchymal stem cell (BMSCs) provide a novel source and a great potential donor cell for regenerative medicine. The current study was set to explore the restorative potential of BMSCs derived exosomes in a rat model of premature ovarian failure (POF) and its underlying mechanisms. Exosomes were prepared and infused to the cisplatin induced POF rats. The ovaries were subjected for histological and immune-histochemical evaluation of survivin and Oct4. RNA extraction and quantitative real time PCR were carried out for evaluation of Stra8, Oct4, Lin28, and Nanos3 gene expression. Serum estradiol (E2) and follicular stimulating hormone (FSH) were monitored. The POF group showed reduced number of follicles, excessive fibrosis, follicular atresia, low serum E2 and high FSH levels compared to controls. BMSCs derived exosomes infusion improved ovarian architecture with normal hormonal profile. There was down and up-regulation of Oct4 and Lin28, markers of stemness and germ cell survival, Stra8 and Nanos3, molecules that judge the cellular fate towards meiosis and oocyte formation in POF, and exosomes treated ovaries respectively. This study demonstrate for the first time that exosomes infusion showed structural and functional reparative properties,possibly through delivering its carriage of protein, molecular content and RNA bioactive molecules to the host ovarian niche inducing neo-oogenesis/folliculogenesis. This provides an effective and novel method for treatment of POF.