Abstract: Diabetic kidney disease (DKD) is a disease of abnormal renal structure and function due to long-term hyperglycemia. Podocyte injury is a major cause of renal inflammation, glomerular filtration barrier injury and renal fibrosis. Ubiquitin proteasome system is involved in intracellular protein clearance. Recent studies have confirmed that it plays an important role in podocyte injury of DKD. High glucose-related injury factors cause an abnormal function of podocyte proteasome, an altered expression level of ubiquitin ligase and an enhancement of deubiquitinating enzyme activity. As a result, an accumulation of injurious protein or an abnormal degradation of protective protein in podocyte may accentuate podocyte injury. This review focused upon the mechanisms of podocyte injury and ubiquitin proteasome involvement in DKD.