Background/Aims: Mouse models are an essential experimental tool for investigating the role of molecular mechanisms and genetic susceptibility in the development of diabetic nephropathy. Methods: The most widely used inbred strain, the C57BL/6 mouse, is commonly used in streptozotocin-induced models of type 1 diabetes and is particularly susceptible to obesity-induced type 2 diabetes. However, use of this strain has been criticised by studies suggesting that it is relatively resistant to renal injury. Results: Recent refinement of these models and utilisation of genetically modified (knockout and transgenic) mice on a C57BL/6 background has provided important insights into the roles of oxidative stress, advanced glycation end products, inflammation and profibrotic mechanisms in the development of type 1 and type 2 diabetic nephropathy. Conclusion: These findings demonstrate the utility of mouse models for identifying and testing novel therapeutic strategies which could translate into better protection against the human disease.