AIM: To identify the related biomarkers, coding genes, transcription factors and biological pathways in diabetic retinopathy(DR)via analysis of the gene expression database of C57BL/KsJ-db/db mice.METHODS: We selected and obtained microarray datasets from the Gene Expression Omnibus database to identify different expressed genes in retinas with db/db mouse model. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology(GO), the construction of a protein-protein interaction network, transcription factor, and gene set enrichment analysis.RESULTS:Totally 38 genes were found upregulated accompanied by down-regulation of 28 genes in the retina of db/db mouse. GO analysis showed that the down-regulated genes were enriched in eye development whereas there was no significant KEGG pathway identified by the differentially expressed genes. The protein-protein interaction network revealed seven hub genes involved in DR. Moreover, GSEA showed 12 up-regulated pathways with 6 down-regulated pathways(P<0.1), predicting up-regulation of 5 transcription factors(TFs)and down-regulation of 8 TFs along with their binding sites. CONCLUSION: The pathways and genes discovered herewith are beneficial to clarify the mechanism of DR and the part of transcription factors identified during the study, such as Runx2, Ppara, MafA, Gata2 and Hoxa13, may provide promising targets for future noval treatment of DR.