In the current review we discuss limitations and recent advances in animal models of diabetic nephropathy (DN). As in human disease, genetic factors may determine disease severity with the murine FVB and DBA/2J strains being more susceptible to DN than C57BL/6J mice. On the black and tan, brachyuric (BTBR) background, leptin deficient (ob/ob) mice develop many of the pathological features of human DN. Hypertension synergises with hyperglycaemia to promote nephropathy in rodents. Moderately hypertensive endothelial nitric oxide synthase (eNOS-/-) deficient diabetic mice develop hyaline arteriosclerosis and nodular glomerulosclerosis and induction of renin-dependent hypertension in diabetic Cyp1a1mRen2 rats mimics moderately severe human DN. In addition, diabetic eNOS-/- mice and Cyp1a1mRen2 rats recapitulate many of the molecular pathways activated in the human diabetic kidney. However, no model exhibits all the features of human DN, therefore researchers should consider biochemical, pathological and transcriptomic data in selecting the most appropriate model to study their molecules and pathways of interest.