Objective：To investigate the expression of miR-296-5p in plasma exosomes of db/db mice with diabetic nephropathy（DN） and explore its role in Snail1-mediated epithelial-mesenchymal transition. Methods：The plasma of 12 12-week-old db/db mice（Model group） and 12 12-week-old db/m mice（Control group） were collected successively，and plasma exosomal RNA was extracted and sequenced. The differential miRNAs targeting Snail1 were summarized by bioinformatics software. Exosomes were identified with transmission electron microscopy and nanoparticle tracking analyzer. The objective miRNA was obtained by screening using kidney tissues and plasma exosomes in db/db mice. The targeting relationship between miR-296-5p and Snail1 was verified by double luciferase experiment. The expression of Snail1，E-cadherin（E-cadherin），and α-smooth muscle actin（α-SMA） were detected in kidney tissues of db/db mice and db/m mice by RT-qPCR and immunohistochemistry. Results：The miR-296-5p was significantly down-regulated in plasma exosomes and kidney of db/db mice，respectively（P=0.011；P=0.001）. The miR-296-5p and Snail1 showed a targeted negative regulation relationship in double luciferase experiment. The gene and protein expression of Snail1 in kidney tissue of db/db mice increased significantly respectively（P < 0.001；P=0.005）. However，the mRNA and protein expression of E-cadherin decreased significantly（P=0.012；P=0.020），while the mRNA expression of α-SMA up-regulated（P=0.042）. Conclusion：The expression of miR-296-5p is down-regulated in plasma exosomes of db/db mice，which may be delivered to renal tubular epithelial cells by plasma exosomes，targeting up-regulated expression of Snail1，and inducing EMT of renal tubular epithelial cells and accelerating renal interstitial fibrosis of DN.