Myocardial　ischemia/reperfusion　(I/R)　injury　is　one　of　the　problems　after　coronary　artery　recanalization　in　patients　with　acute　myocardial　infarction,　and　the　discovery　of　exosomes　presents　a　broad　potential　for　treating　myocardial　I/R　injury.　This　work　examined　the　function　and　regulatory　mechanisms　of　exosomes　produced　from　bone　marrow　mesenchymal　stem　cells　(BMSCs-Exo)　in　myocardial　I/R　injury.　Rats　with　I/R　injuries　had　their　myocardium　directly　injected　with　BMSCs-Exo.　The　outcomes　demonstrated　that　cardiac　function　was　enhanced　and　BMSCs-Exo　dramatically　decreased　myocardial　infarct　size.　Transcriptome　sequencing　was　performed　on　heart　tissues　from　the　model　and　exosome-treated　groups.　GO　and　KEGG　enrichment　analyses　revealed　that　exosomes　might　mitigate　myocardial　I/R　damage　via　the　AMPK/PGC-1　alpha　signaling　pathway,　confirmed　by　both　in　vitro　and　in　vivo　tests.　The　findings　imply　that　compound　C　and　sh-AMPK　reverse　the　activation　of　PGC-1　alpha　and　its　downstream　proteins　and　negate　the　protective　effects　of　exosomes　against　oxidative　stress　and　mitochondrial　function　in　damaged　cardiomyocytes.　On　the　other　hand,　p-AMPK　expression　was　unaffected　by　PGC-1　alpha　silencing.　It　was　demonstrated　that　via　activating　the　AMPK/PGC-1　alpha　signaling　pathway,　BMSCs-Exo　might　reduce　oxidative　stress　and　mitochondrial　dysfunction　in　cardiomyocytes,　thereby　protecting　against　myocardial　I/R　damage.