Abstract: Objective To explore the key genes of diabetic nephropathy(DN) and renal tubulointerstitial fibrosis(RTF) and examine their clinical correlations by bioinformatic analysis.Methods The datasets of renal interstitial tissue from DN and non-DN patients and renal tissue from RTF model mice were downloaded for identifying differentially expressed genes(DEGs) and screening DN specific RTF related genes.Functional enrichment and protein-protein interaction(PPI) analysis was performed for further identifying key genes.Pearson’s correlation analysis between key genes and renal function was conducted for elucidating the clinical relevance of the key genes.Results A total of 125 DN specific RTF related genes were identified.Biological function enrichment analysis showed that the above genes were correlated with immune response and metabolic process and became enriched in Toll-like receptor,NF-kappa B,tumor necrosis factor(TNF) and chemokine pathways.Based upon PPI network analysis,ITGAM,TLR2,LCP2,TLR7 and IL10RA were identified as key genes.Fold change of gene expression level was significantly higher in DN group than that in control group.And the area under curve(AUC) was 1,0.925,0.9583,0.9583 and 0.8833 respectively(P＜0.01).Pearson’s correlation coefficients(r value) between gene expression level of key genes and estimated glomerular filtration rate(eGFR) were -0.7956,-0.6463,-0.752,-0.7136 and -0.7721 respectively(P＜0.05).Conclusion Key genes correlated with DN specific RTF are identified.Negatively correlated with eGFR,they may participate in the process of DN-RTF through immune-inflammatory responses.