With the delay of female childbearing age, the need for treatment of premature ovarian insuffi-ciency (POI) in women aged 30~39 is increasing. Previous studies confirmed that different tissue-derived stem cells could restore ovarian function of POI mice. The purpose of this study was to explore the efficacy and underlying mechanisms of human placenta-derived mesenchymal stem cell (hpMSC) transplantation for incre-mental load training-induced POI. After establishment of a POI rat model by 9-week treadmill training with incremental load, the POI rats were administered with hpMSCs by tail vein injection. Ovarian function was evaluated by detection of hormone levels and histological analysis. hpMSC tracking, enzyme linked im-munosorbent assay (ELISA), Western-blot, immunohistochemistry staining, and real-time fluorescence quan-titative PCR were used to assess the molecular mechanisms of ovarian function injury and repair. The results showed that hpMSCs colonized the ovarian stroma. hpMSC transplantation increased oocyte telomere length, reduced oxidative stress, downregulated Bcl-2-associated X protein (Bax) and caspase-3 expression levels. In addition, after transplantation, the follicle-stimulating hormone (FSH) levels and ratio of FSH to luteinizing hormone (FSH/LH) decreased, and the number of follicles at all stages increased. These results demonstrated that hpMSC transplantation could repair ovarian injury and improve ovarian function in incremental load training-induced POI rats.