Diabetic nephropathy (DN) is a crucial microvascular complication of diabetes. Long non-coding RNAs (lncRNAs) participate in the occurrence and development of various diseases, but the function and regular mechanism of lncRNA-NR_033515 in DN is still unclear. In the present study, we demonstrated that the expression of NR_033515 was significantly increased in the serum of DN patients and was related to the different stages of DN. NR_033515 was also positively associated with diagnostic markers of DN (KIM-1 and NGAL). Overexpression of NR_033515 promoted proliferation, and inhibited apoptosis of MMC cells and increased the expression levels of proliferation-related genes. NR_033515 also accelerated the expression levels of fibrogenesis-related genes. TGF-β1 enhanced NR_033515-induced Epithelial-mesenchymal transition (EMT), while NR_033515 over-expression accelerated TGF-β1-induced EMT. Furthermore, we found that NR_033515 promoted cell proliferation and regulated P38, ASK1, Fibronectin, α-SMA, E-cadherin, and Vimentin expressions by miR-743b-5p. Therefore, our data indicated the potential role of NR_033515 in the proliferation, fibrogenesis and EMT in DN. NR_033515 could be a pivotal potential diagnostic and therapeutic target for the treatment of DN.