Transplantation of cryopreserved ovarian tissue is a novel technique to restore endocrine function and fertility especially for cancer patients. However, the main obstacle of the technique is massive follicle loss as a result of ischemia in the process of transplantation. Mesenchymal stem cells (MSCs) have been acknowledged to play an important role in supporting angiogenesis and stabilizing long-lasting blood vessel networks through release of angiogenic factors and differentiation into pericytes and endothelial cells. This study is aimed to investigate whether MSCs could be applied to overcome the above obstacle to support the ovarian tissue survival in the transplantation. Here we show that human MSCs could enhance the expression level of VEGF, FGF2, and especially the level of angiogenin, significantly stimulate neovascularization, and increase blood perfusion of the grafts in the cryopreserved ovarian tissue transplantation. Further studies reveal that MSCs could notably reduce the apoptotic rates of primordial follicles and decrease follicle loss in the grafted ovarian tissues. In summary, our findings demonstrate a previously unrecognized function of MSCs in improving human ovarian tissue transplantation and provide a useful strategy to optimize fertility preservation and restoration.