〔Abstract〕 Objective To investigate the role of Krüppel-like factor 4（KLF4）in type 1 diabetic nephropathy（DN）and to elucidate its underlying mechanisms. Methods Sixteen male Sprague-Dawley（SD）rats were se⁃lected and randomly divided into control group and model group，with 8 rats in each group. Rats in model group were intraperitoneally injected with a single dose of 55 mg/kg streptozotocin（STZ）to establish a diabetic nephropa⁃thy（DN）model，while those in control group were injected with an equal volume of sodium citrate buffer at the same time. After successful model establishment，the serum levels of blood urea nitrogen（BUN）and serum creati⁃ nine（SCR）were determined. Hematoxylin-eosin（HE）staining was performed on renal tissues to observe patho ⁃ logical changes，and immunofluorescence staining was conducted to detect the expression of KLF4 in renal tissues. Lipid peroxidation levels were evaluated by measuring malondialdehyde（MDA），Fe²⁺，and lipid peroxidation prod⁃ucts in rat kidneys. A high glucose（HG）-induced cell injury model was established in HK-2 cells，with mitochon⁃ drial membrane potential assessed using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine io ⁃ dide（JC-1）staining. Lipid peroxidation levels（MDA，Fe²⁺，and lipid peroxides）were measured in HK-2 cells. KLF4-overexpressing HK-2 cells were then constructed，followed by repeated JC-1，MDA，Fe²⁺，and lipid peroxi⁃ dation assays. Western blot was performed to evaluate the expression of ferroptosis-related proteins including gluta-thione peroxidase 4（GPX4），nuclear factor erythroid 2-related factor 2（NRF2），and Kelch-like ECH-associated protein 1（Keap1），in renal tissues，HK-2 cells，and KLF4-overexpressing HK-2 cells. Results Compared with the control group，DN rats exhibited elevated serum BUN and SCR levels，glomerular hypertrophy，renal intersti⁃ tial fibrosis，and decreased KLF4 expression. Additionally，MDA，Fe²⁺，and lipid peroxidation levels increased， indicating enhanced ferroptosis in renal tissues，accompanied by reduced GPX4 and NRF2 expression and elevated Keap1 levels. Similarly，HG-treated HK-2 cells showed decreased KLF4 expression，increased MDA，Fe²⁺ and lipid peroxidation，elevated ferroptosis，and dysregulated GPX4/NRF2/Keap1 expression. However，KLF4 overex⁃ pression reversed these alterations induced by high glucose treatment. Conclusion In the renal tissues of type 1 diabetic rats，the expression of KLF4 decreases the level of ferroptosis increases，and KLF4 overexpression could alleviate HG-induced HK-2 cell injury.