Renal ischemia-reperfusion (I/R) is one of the main causes of the acute kidney injury (AKI) that usually occurs during clinical surgery. Autophagy plays an important role in recovery from acute ischemic kidney injury. MicroRNA-21 (miR-21) was reported to inhibit autophagy in several diseases. However, the molecular mechanism of miR-21 on autophagy during renal I/R is still unclear. For the in vitro study, NRK-52E cells were transfected with miR-21 mimics and subjected to I/R. Results showed that miR-21 mimics inhibited cell viability and induced cell apoptosis in NRK-52E cells. Expression of beclin-1 and LC3-II was induced, and p62 was decreased by I. miR-21 mimics inhibited this induction. RT-PCR and western blotting assay showed that miR-21 mimics inhibited the protein level of Rab11a, but not the mRNA level. A luciferase activity assay showed that miR-21 directly targeted Rab11a Rab11a overexpression attenuated the effect of miR-21 mimics and I/R on cell viability and cell apoptosis. The expression of beclin-1 and LC3-II was increased, and p62 was decreased by Rab11a overexpression. For the in vivo assay in a rat I/R model, the miR-21 level was increased during renal I/R injury. Pre-treatment with miR-21 inhibitor injection attenuated the renal injury, and enhanced expression of LC3-II and beclin-1. The results showed that miR-21 inhibited autophagy by targeting Rab11a in renal I/R, indicating that Rab11a might be a new medical target for the treatment of renal I/R. (C) 2015 Elsevier Inc. All rights reserved.