Inflammation is a protective response to remove dangerous stimuli from the body. The multiprotein complex called the inflammasome regulates inflammation through the cleavage of proinflammatory cytokines into mature forms. Shahzad et al. unravel the importance of the Nlrp3 inflammasome, especially activated in glomerular resident cells, in diabetic nephropathy. They also show the role of mitochondrial reactive oxygen species as a mediator to activate the inflammasome in diabetic conditions. Targeting the inflammasome could be a promising approach for diabetic nephropathy.