FMS-like　receptor　tyrosine　kinase　3　(Flt3)　expression　was　reported　to　increase　in　the　heart　in　response　to　pathological　stress,　but　the　role　of　Flt3　activation　and　its　underlying　mechanisms　remain　poorly　elucidated.　This　study　was　designed　to　investigate　the　role　of　Flt3　activation　in　sympathetic　hyperactivity-induced　cardiac　hypertrophy　and　its　mechanisms　through　autophagy　and　mitochondrial　dynamics.　In　vivo,　cardiac　hypertrophy　was　established　by　subcutaneous　injection　of　isoprenaline　(6　mg/kg　center　dot　day)　in　C57BL/6　mice　for　7　consecutive　days.　The　Flt3-ligand　intervention　was　launched　2　h　prior　to　isoprenaline　each　day.　In　vitro,　experiments　of　cardiomyocyte　hypertrophy,　autophagy,　and　mitochondrial　dynamics　were　performed　in　neonatal　rat　cardiomyocytes　(NRCMs).　Our　results　revealed　that　the　expression　level　of　Flt3　protein　was　significantly　increased　in　the　hypertrophic　myocardium　provoked　by　isoprenaline　administration.　Flt3-ligand　intervention　alleviated　isoprenaline-induced　cardiac　oxidative　stress,　hypertrophy,　fibrosis,　and　contractile　dysfunction.　Isoprenaline　stimulation　impaired　autophagic　flux　in　hypertrophic　mouse　hearts,　supported　by　the　accumulation　of　LC3II　and　P62　proteins,　while　Flt3-ligand　restored　the　impairment　of　autophagic　flux.　Flt3　activation　normalized　the　imbalance　of　mitochondrial　fission　and　fusion　in　the　hearts　of　mice　evoked　by　isoprenaline　as　evidenced　by　the　neutralization　of　elevated　mitochondrial　fission　markers　and　reduced　mitochondrial　fusion　markers.　In　NRCMs,　Flt3-ligand　treatment　attenuated　isoprenaline-stimulated　hypertrophy,　which　was　abolished　by　a　Flt3-specific　blocker　AC220.　Activating　Flt3　reversed　isoprenaline-induced　autophagosome　accumulation　and　impairment　of　autophagic　flux　probably　by　enhancing　SIRT1　expression　and　consequently　TFEB　nuclear　translocation.　Flt3　activation　improved　the　imbalance　of　mitochondrial　dynamics　induced　by　isoprenaline　in　NRCMs　through　the　SIRT1/P53　pathway.　Activation　of　Flt3　mitigated　ISO-stimulated　hypertrophy　probably　involves　the　restoration　of　autophagic　flux　and　balance　of　mitochondrial　dynamics.　Therefore,　activation　of　Flt3　attenuates　isoprenaline-induced　cardiac　hypertrophy　in　vivo　and　in　vitro,　the　potential　mechanism　probably　attributes　to　SIRT1/TFEB-mediated　autophagy　promotion　and　SIRT1/P53-mediated　mitochondrial　dynamics　balance.　These　findings　suggest　that　activation　of　Flt3　may　be　a　novel　target　for　protection　against　cardiac　remodeling　and　heart　failure　during　sympathetic　hyperactivity.