Aim:　Type　2　diabetes　mellitus　(T2DM)　is　one　of　the　most　common　diseases,　and　epigenetic　modification　N6-methyladenosine　(m6A)　is　essential　for　transcriptional　modulation　involved　in　its　development.　However,　the　precise　role　and　landscape　of　transcriptome-wide　m6A　alterations　in　molecular　adaptations　after　physical　exercise　have　yet　to　be　fully　elucidated.　Methods:　Four-week-old　male　C57BL/6J　mice　received　a　high-fat　diet　(HFD)　for　12　weeks　to　establish　a　diabetic　state,　and　HFD　mice　were　simultaneously　subjected　to　physical　exercise　(HFD　+　EX).　The　hepatic　RNA　m6A　methylome　was　examined,　the　conjoint　MeRIP-seq　and　RNA-seq　was　performed,　and　the　exercise-modulated　genes　were　confirmed.　Results:　Physical　exercise　significantly　ameliorates　liver　metabolic　disorder　and　triggers　a　dynamic　change　in　hepatic　RNA　m6A.　By　analyzing　the　distribution　of　m6A　in　transcriptomes,　an　abundance　of　m6A　throughout　mRNA　transcripts　and　a　pattern　of　conserved　m6A　after　physical　exercise　was　identified.　It　is　noteworthy　that　conjoint　MeRIP-seq　and　RNA-seq　data　revealed　that　both　differentially　methylated　genes　and　differentially　expressed　genes　were　enriched　in　all　stages　of　the　PI3K-Akt　signaling　pathway,　in　particular　the　upstream　nodes　of　this　pathway,　which　are　considered　a　valuable　therapeutic　target　for　T2DM.　Moreover,　in vivo　and　in vitro　analyses　showed　that　exercise-mediated　methyltransferase　Rbm15　positively　regulated　the　expression　of　two　upstream　genes　(Itga3　and　Fgf21)　in　an　m6A-dependent　manner.　Conclusion:　These　findings　highlight　the　pivotal　role　of　the　exercise-induced　m6A　epigenetic　network　and　contribute　insights　into　the　intricate　epigenetic　mechanism　underlying　insulin　signaling.　©　2024　The　Authors.　Acta　Physiologica　published　by　John　Wiley　&　Sons　Ltd　on　behalf　of　Scandinavian　Physiological　Society.