Background: Egr1 and renin-angiotensin system(RAAS)are invlovled in DKD, but the relationship between them is unclear. Methods: Egr1 and RAAS were detected in HFD/STZ-induced mice and HK-2 cells treated with TGF-β1. Then, RAAS expression was detected in HK-2 cells and mice with overexpression and knock-down of Egr1. The direct relationship between Egr1 and RAAS was explored via ChIP assay. Results: We found increased levels of Egr1 and RAAS in the kidney cortices of DKD mice and TGF-β1-treated HK-2 cells. Overexpression or silencing of Egr1 in HK-2 cells and DKD mice could upregulate or downregulate the expression of RAAS. ChIP assays revealed that TGF-β1 induced Egr1 to bind to the RAAS promoter. Conclusions: Our study provides strong evidence that Egr1 is a transcriptional activator of RAAS in DKD. Disclosure Y. Xue: None.