Toll-like Receptor 4 (TLR4) may play an important role in the pathogenesis of diabetic nephropathy (DN). In this study, We observed the TLR4 signal and the release of inflammation factors after angiotensin II (Ang II) stimulation in rat mesangial cells (MCs) under high glucose conditions, this revealed the innate immune mechanism of injury by Ang II in DN. Our data showed that TLR4 and MyD88 were up-regulated significantly in high glucose and AngII-induced MCs; meanwhile, NF-kappa B as well as MCP-I, IL-6 were also highly expressed. In cells that were transfected with TLR4 SiRNA, the parameters were greatly inhibited; similar effects were detected in cells that were treated with Irbesartan. We concluded that Ang II synergized with high glucose in the release of pro-inflammatory factors mainly through the upregulation of TLR4 signaling in MCs, Cross-talk between Ang II and TLR4 contributed to the MC inflammatory injury under high glucose conditions. (C) 2015 Elsevier Inc. All rights reserved.