Type 2 diabetes mellitus (T2dM) is a disease associated with a number of metabolic disturbances, including protein metabolism. In the present study, blood samples were obtained from Bahraini subjects, including 6 patients with T2dM and 6 age- and sex-matched, non-diabetic, healthy controls. depleted and non-depleted sera were prepared from the collected blood, and the global protein expression changes were evaluated by liquid chromatography tandem mass spectrometry. Only significantly and markedly differentially-expressed proteins (P<0.05, analysis of variance; maximum fold change ≥1.5) were considered as candidate proteins for informatics analysis. Accordingly, a total of 62 proteins were identified to be differentially expressed in T2dM, compared with control subjects, and they were grouped functionally into 16 classes of proteins. The largest class was that of the immune-associated proteins. Additionally, ~25 of these proteins (40%) had previously been associated with dM; however, the association of the other 37 proteins with T2dM was a novel observation. The majority of the identified proteins were upregulated in T2DM. The identified proteins could be involved in the pathogenesis of the disease or serve as disease biomarkers. Further validation of the identified proteins in a large study cohort is required, in order to fully access their potential clinical usefulness. © 2019 Spandidos Publications. All rights reserved.