The gold standard for differential diagnosis of diabetic nephropathy and non-diabetic renal disease is the pathology of renal biopsy. It′s difficult for patients to accept the renal biopsy as an invasive examination. Thus, in clinical practice, clinicians often make the differential diagnosis based on diabetic retinopathy, proteinuria, diabetes duration, hematuria, and systolic blood pressure, etc. In recent years, a mounting understanding for the traditional clinical indicators has appeared. At the same time, new noninvasive biomarkers and imaging techniques contributing to differential diagnosis have also increased. All of these new findings have provided a broader horizon for the differential diagnosis of diabetic kidney diseases.