Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions.