Proteomic methods have found broad applications in kidney disease research and more specifically in diabetic nephropathy (DN) research. Proteomic methods such as 2-dimensional gel electrophoresis have been used to gain insight into glomerular and tubular nephropathies including DN. At the protein level, differences in high-abundant proteins in DN have been shown to reflect primarily differentially posttranslationally modified plasma proteins. Higher-sensitivity proteomic methods (eg, liquid chromatography-mass spectrometry) have pushed the boundaries on the known urinary proteome to include more than 1,500 proteins. These same high-sensitivity methods have been applied toward profiling urinary peptides, which has resulted in methods to diagnostically screen urine to differentiate between type-2 diabetes mellitus and type-1 diabetes mellitus urine, normal versus microalbuminuria, or by angiotensin II receptor blocker treatment. Proteomic methods are being used to show response to insulin gene therapy in an animal model or alterations in the renal cortex mitochondrial proteome with the development of the diabetic phenotype. Proteomic methods continue to aid in the discovery of new mechanisms of diabetic pathology and understanding of the etiology of diabetic complications.