Ischemic stroke (IS) remains a significant global health burden, necessitating the development of novel therapeutic strategies. This study aims to systematically evaluate the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Exos) on IS outcomes in rodent models.A comprehensive literature search was conducted across multiple databases to identify studies investigating the effects of MSC-Exos on rodent models of IS. Following rigorous inclusion and exclusion criteria, 73 high-quality studies were selected for meta-analysis. Primary outcomes included reductions in infarct volume/ratio and improvements in functional recovery scores. Data extraction and analysis were performed using RevMan 5.3 software.Pooled data indicated that MSC-Exos administration significantly reduced infarct size and improved functional recovery scores in rodent models of IS. Treatment within 24 hours and beyond 24 hours of stroke induction both demonstrated substantial reductions in infarct volume/ratio compared to controls. Furthermore, MSC-Exos-treated groups exhibited marked improvements in functional recovery, as assessed by various neurobehavioral tests. The meta-analysis showed no significant publication bias, and heterogeneity levels were acceptable.MSC-Exos reveal significant therapeutic potential for IS, with evidence supporting their efficacy in reducing infarct size and enhancing functional recovery in preclinical rodent models. These findings pave the way for further research and potential clinical translation.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.