This study aims to screen key genes related to diabetic encephalopathy(DE)，potential targets of the genes，and biological processes and pathways of the genes based on bioinformatics，and thereby predict potential effective Chinese medicinals.Methods:The microarray dataset GSE161355 was screened from Gene Expression Omnibus(GEO) for analysis.Differently expressed genes were yielded based on quality evaluation and difference analysis by R Studio，and DAVID was employed for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis.Cytoscape was applied to screen key targets and visualize key functional modules.By mapping key targets with the Coremine Medical，we screened potential Chinese medicinals for the treatment of DE，and constructed the “potential medicinal-active component-core target” network.Results:A total of 326 significantly differential genes were screened out，which were involved in the biological processes such as learning，memory，synaptic transmission of neurons，cell division，protein secretion，and angiogenesis regulation，and the pathways of neural active ligand-receptor interaction，cell cycle，and other pathways.The protein-protein interaction(PPI) network showed MCHR2，CXCR2，GNAI1，P2RY13，NPY1R，C3，LPAR4，OXTR，CHRM5，CDC7，ORC5，ORC4，and CCNA1 were potential targets against DE，which were involved in inflammation，cell apoptosis，endoplasmic reticulum stress，angiogenesis，and other biological processes from multiple aspects.Radix Ginseng，Radix Rehmanniae Preparata，Stigma Croci，Folium Ginkgo，Rhizoma Coptidis，and Radix Curcumae were effective medicinals，which nourish qi，blood，yin and yang，promote blood circulation，remove blood stasis，dredge collaterals，resolve phlegm，refresh the brain，and resuscitate.Conclusion:This study further clarified the pathogenesis of DE through the analysis of differentially expressed genes and potential core targets，which provides a new theoretical research direction and clinical basis for future treatment and prognosis evaluation.