Diabetic nephropathy (DN) is a common and characteristic microvascular complication of diabetes; the mechanisms that cause DN have not been clarified, and the epigenetic mechanism was promised in the pathology of DN. Furthermore, ubiquitination and small ubiquitin-like modifier (SUMO) were involved in the progression of DN. MG132, as a ubiquitin proteasome, could improve renal injury by regulating several signaling pathways, such as NF- κ B, TGF- β , Nrf2-oxidative stress, and MAPK. In this review, we summarize how ubiquitination and sumoylation may contribute to the pathology of DN, which may be a potential treatment strategy of DN.