Objective: To obtain the key genes and signal pathways of diabetic peripheral neuropathy (DPN) through bioinformatics analysis of related gene chips in the GEO database. Methods: The DPN-related gene chip was downloaded from the GEO database, and the differential genes (DEGs) between DPN female patients and the normal control group were analyzed and visualized using R language. According to the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), DEGs were annotated, their functions and related pathways were predicted, and a protein interaction network was constructed using the STRING database to screen for core genes. Results: The analysis chip GSE95849 obtained 4746 DEGs of which 2218 genes were up-regulated and 2528 genes were down-regulated. Among them, TFAP2C, ESR1, CX3CR1, and FGL2 are at the core site of protein interaction. Conclusions: Differential genes are mainly involved in the MAPK pathway. They participate in the pathogenesis of DPN through blood glucose homeostasis, inflammatory effects, and neuronal development, providing new ideas for the diagnosis and treatment of DPN.