Diabetic nephropathy (DN) is the major reason for end stage renal disease in the western world. Patients with DN developed more severe cardiovascular complications with worse prognosis. In spite of tight blood pressure and glucose control through applying angiotensin II receptor antagonism, angiotensin receptor inhibitors and even direct renin inhibitors, the progression and development of DN has continued to accelerate. Nuclear receptors are, with few exceptions, ligand-depended transcription factors some of which modulate genes involved in the transportation and metabolism of carbohydrate or lipid, and inflammation. Considering the diverse biological functions of nuclear receptors, efforts have been made to explore their contributions to the pathogenesis of DN and potential therapeutic strategies. This review is mainly focused on the association between various nuclear receptors and the pathogenesis of DN, the potential beneficial effects of targeting these receptors for preventing the progress of DN, and the important role that nuclear receptors may play in future therapeutic strategies for DN.