Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia. The liver has a critical role in regulating glucose homeostasis. The present study aimed to analyze hepatic gene expression profiles and to identify the key genes and pathways involved in T2DM. Gene expression profiles of 10 patients with T2DM and 7 subjects with normal glucose tolerance were downloaded from the Gene Expression Omnibus database. Subsequently, differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed. In addition, a protein-protein interaction network was built and hub genes were identified. In total, 1,320 DEGs were identified, including 698 up- and 622 downregulated genes, and these were mainly enriched in positive regulation of transcription from RNA polymerase II promoter, cell adhesion, inflammatory response, positive regulation of apoptotic process, signal transduction and the Tolllike receptor signaling pathway. A total of 8 hub genes (G-protein subunit gamma transducin 2, ubiquitinconjugating enzyme E2 D1, glutamate metabotropic receptor 1, G-protein signaling modulator 1, C-X-C motif chemokine ligand 9, neurotensin, purinergic receptor P2Y1 and ring finger protein 41) were screened from the network. The present study may contribute to the elucidation of the hepatic pathology of T2DM. Copyright: © Chen et al.