<p>ObjectiveTo investigate the therapeutic effects and underlying mechanisms of umbilical cord mesenchymal stem cells (UCMSCs) on chemotherapy-induced premature ovarian insufficiency (POI) in rats. Methods. A POI rat model was established using cyclophosphamide (CTX). Female Sprague Dawley rats were randomly allocated into five experimental groups and treated with varying concentrations of UCMSC transplantation via tail vein injection. Ovarian function and apoptotic activity were evaluated through comprehensive assessment including serum hormonal profiling, histopathological examination, and molecular characterization. Results Compared to controls, the CTX-treated model group demonstrated severe ovarian dysfunction characterized by reduced ovarian mass, disrupted estrous cycles, and abnormal serum hormone levels. UCMSC transplantation produced dose-dependent restoration of ovarian physiology, with the highest dose achieving near-complete functional recovery. Molecular analyses revealed that UCMSCs dose-dependently modulated apoptosis-related gene expression, characterized by upregulated BCL2 and downregulated BAX and Caspase-3 levels. Additionally, UCMSCs suppressed P53 phosphorylation while simultaneously increasing AKT phosphorylation levels, indicating activation of pro-survival signaling pathways. Conclusion UCMSC transplantation effectively mitigates chemotherapy-induced ovarian injury and improves ovarian function, likely through suppressing ovarian cell apoptosis. The therapeutic mechanism appears to involve suppression of pro-apoptotic P53 signaling coupled with enhanced PI3K-AKT pathway activation. These findings highlight UCMSCs as a promising therapeutic strategy for POI management.</p>