Premature ovarian failure (POF) contributes significantly to female infertility in young women. It mainly developed after chemotherapy medication, particularly with alkylating cytotoxic such as cyclophosphamide (CYP). The present study was designed to determine the advantages of mesenchymal stem cells (MSCs) as therapy for POF conditions in female rat models. For POF induction, CYP (200mg/Kg b.wt) was injected intraperitoneally (i.p) followed by another activation dose of CYP (10mg/ b.wt, i.p) after one week. MSCs treatment was enhanced by Bone Marrow-derived stem cells (BM-MSCs) or Umbilical Cord-derived stem cells (UC-MSCs) after two weeks of POF induction. The normal control (NC) group rats were injected with saline. The effects of POF modeling and MSCs (1 × 106 cells) transplantation through tail-vein were examined by sex hormonal analysis and morphological examination of ovarian follicles. CYP-induced rats POF showed a significant reduction in AMH and E2 concentrations in addition to total, primordial, primary, secondary, and mature graffian follicles in contrast to the NC group (P