To assess the effect of exosomal <i>miR-27a-3p</i> on MMT and renal fibrosis, additional <i>in vitro</i> and <i>in vivo</i> investigations were conducted.<h4>Results</h4>Renal IRI increased exosome secretion, promoted MMT, and exacerbated renal fibrosis, whereas <i>BMAL1</i> overexpression or <i>Rab27a</i> knockout significantly attenuated IRI-induced MMT and fibrotic progression. Here, RAB27A is linked to renal fibrosis.