Purpose: To investigate the protective effects of miR-301 in exosomes secreted by bone mesenchymal stem cells (BMSCs) on rats' myocardial infarction (MI). Methods: After isolation and culture, BMSCs were identified using flow cytometry. Then exosomes were then isolated. Rats MI models were established and they were divided into 4 groups: Sham group, Model group (injected with PBS), BMSC-Exos group (injected with exosomes secreted by BMSCs), BMSC-301-Exos group (injected with exosomes secreted by BMSCs transfected with miR-301 mimics). Cardiac function was assessed by cardiac echocardiography. Myocardial infarct area was measured by Masson trichrome staining mRNA and proteins expression were measured by qRT-PCR and western blot. Exosome morphology and myocardial cells autophagy were observed by transmission electron microscopy. Results: BMSCs were obtained. Rat MI models were successfully established. After rats were injected with exosomes secreted by BMSCs transfected with miR-301 mimics, MI tissues were found to have much higher miR-301 expression, LVEF, LVFS, P62 expression, and remarkably lower LVESD, LVEDD, MI area, LC3-II/LC3-I ratio and autophagosomes numbers compared with BMSC-Exos group (all P<0.05). Conclusion: miR-301 in exosomes secreted by BMSCs protected MI by inhibiting myocardial autophagy. (C) 2019 Elsevier Inc. All rights reserved.