The aim of this study was to deeply explore the pathogenesis of obesity type 2 diabetes mellitus (O-T2DM) and search for potential biomarkers through high-throughput RNA sequencing technology. The study included 15 patients with O-T2DM and 15 healthy controls, and peripheral blood samples were collected for transcriptome analysis. The results showed that compared with the control group, there were 442 circRNAs and 2756 mRNAs with significant differential expression in the O-T2DM group. Through weighted gene co-expression network analysis (WGCNA) and pathway enrichment analysis, it was found that the differentially expressed mRNAs were mainly enriched in signaling pathways such as T cell receptor, cell senescence, cytotoxicity mediated by NK cells, IL-17, lipids and atherosclerosis, and the oxidative phosphorylation pathway was activated, and apoptosis was inhibited. Based on the ceRNA theory, a regulatory network was constructed, and key circRNAs such as hsa_circ_0060614 were screened out, which may regulate the expression of the MT2A gene by adsorbing hsa-mir-4668-3p, and the expression levels of the three were significantly increased in O-T2DM patients. This study provides a new perspective for the research on the molecular mechanism of O-T2DM and an important theoretical basis for the development of personalized treatment and precision medicine for it.