Emerging evidence have indicated the vital roles of long noncoding RNAs (IncRNAs) in the pathophysiological process of diabetic nephropathy. However, the deepgoing mechanism that IncRNAs regulate the diabetic nephropathy pathogenesis is still ambiguous. In present study, we found that IncRNA LINC00968 expression was high-expressed in the diabetic db/db mouse tissue and high-glucose induced mesangial cells. Functional experiments indicated that LINC00968 silencing by siRNAs significantly inhibited the proliferation and cycle progression, and decreased the extracellular matrix (ECM) proteins (fibronectin, collagen IV) expression in the high glucose induced of mesangial cells. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assay revealed that LINC00968 recruit EZH2 to the promoter of p21 to inhibit its expression. In summary, our results support the conclusion that IncRNA LINC00968 accelerates the proliferation and fibrosis of mesangial cells by epigenetically repressing p21 via recruiting EZH2, providing a novel insight for the diabetic nephropathy pathogenesis. (C) 2018 Elsevier Inc. All rights reserved.