In the current study, we applied the RNA sequencing technology for the peripheral blood Ropinirole mononuclear cells RNA of RA and T2D patients to study the gene expression changes and identify the differentially expressed genes by comparison with healthy volunteers. Furthermore, we performed bioinformatics analysis and network analysis to identify the associated pathways of RA and T2D. Several studies reported the associations between RA andT2D, but the overall molecular pathways and network associations between the two disease conditions have not been established. This analysis of PBMC gene profiles in RA, T2D and healthy persons by DGE showed the unique and Skepinone-L shared gene expression signatures to explain the associations of the two chronic complex diseases further at the transcriptome level. We identified 212 DEGsinRA patients and 114 DEGsinT2D patients compared with healthy volunteers, respectively. 32DEGs commonly shared in DGE profiles of both RA vs. control and T2Dvs.control groups. Based on the shared top10signalingpathways, top10biofunctions, 5 predicted upstream regulators, and the shared DEGs involved in, we summarized the shared molecular paths between RA and T2D related with immune response. The complement system constitutes an important component of the defense against foreign organisms, functioning both in innate and adaptive immune systems, which is potentially harmful also to the own organism. There was strong evidence implied that both the classical and the alternative pathways of complement are pathologically activated during RA. There was also a high level of complements in both types of diabetes mellitus. Same with other reports, the complement system was found as one of the most important shared signaling pathway between RA and T2D in this study. The up-regulated DEG C4BPA participated in complement system signaling, indicated the activation of complement system in both RA and T2D. C4b-binding protein is the most important soluble regulator of the classical pathway of complement activation, one major form of which is C4BP-alph. Invitro studies demonstrate that IL-6, IL-1beta, and IFN-gamma increase the levels of C4BPA mRNAs.