Accumulating evidence supports intrinsic genetic susceptibility as an important variable in the progression of diabetic nephropathy in people. Mice provide an experimental platform of unparalleled power for dissecting the genetics of mammalian diseases; however, phenotypic analysis of diabetic mice lags behind that already established for humans. Standardized benchmarks of hyperglycemia, albuminuria, and measurements of renal failure remain to be developed for different inbred strains of mice. The most glaring deficiency has been the lack of a diabetic mouse model that develops progressively worsening renal insufficiency, the sine qua non of diabetic nephropathy in humans. Differences in susceptibility of these inbred strains to complications of diabetes mellitus provide a possible avenue to dissect the genetic basis of diabetic nephropathy; however, the identification of those strains and/or mutants most susceptible to renal injury from diabetes mellitus is lacking. Identification of a mouse model that faithfully mirrors the pathogenesis of DN in humans will undoubtedly facilitate the development of new diagnostic and therapeutic interventions.