Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus and often results in chronic renal failure. Here, we found that Interleukin 1 receptor associated kinases (IRAK1) was up-regulated in kidney in both DN patients and high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. In vivo, down regulation of IRAK1 ameliorated renal injury and function, with lower podocyte apoptosis, increased expression of Nephrin, attenuated thickness of the glomerular basement membrane and podocyte footprocess effacement. Furthermore, in vitro, down regulation of IRAK1 in podocytes treated with high glucose (HG), podocyte apoptosis and inflammatory cytokines were significantly decreased, but Nephrin increased. Meanwhile, apoptosis-related genes caspase-3/-9 were inhibited and phosphorylation levels of PI3K/Akt were dramatically down regulated. Thus, IRAK1 is one of the critical components involved in podocyte apoptosis in DN. (C) 2018 Elsevier Inc. All rights reserved.