Inflammation is an important, yet poorly understood cause of renal damage in diabetic nephropathy. Nlrp3-inflammasome activation has now been demonstrated in endothelial cells and podocytes from patients with diabetes in vitro, and in mouse models of diabetes. Nlrp3-inflammasome-mediated damage did not arise from circulating immune cells. Nlrp3 or CASP1 knock out and IL-1 receptor antagonism all protected against diabetic nephropathy in mouse models of diabetes. This research identifies several potential targets for diabetic nephropathy treatment.