It is suggested that cytokines play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM). Therefore, this study explored two recently discovered cytokines, interleukin (IL)-37 (anti-inflammatory) and IL-39 (pro-inflammatory), in T2DM due to limited data in this context. Serum IL-37 and IL-39 levels were determined in 106 T2DM patients and 109 controls using enzyme-linked immunosorbent assay kits. Serum levels (median and interquartile range) of IL-37 (79 [47-102] vs. 60 [46-89] ng/L; probability [p]=.04) and IL-39 (66 [59-69] vs. 31 [19-42] ng/L; p< .001) were significantly elevated in T2DM patients compared to controls. As indicated by the area under the curve (AUC), IL-39 (AUC=0.973; p< .001) was more predictable for T2DM than IL-37 (AUC=0.582; p= .039). Elevated levels of IL-39 were significantly associated with T2DM (odds ratio=1.30; p< .001), while IL-37 did not show this association. Classification of IL-37 and IL-39 levels by demographic and clinical characteristics of patients revealed some significant differences including gender (IL-39), body mass index (BMI; IL-37 and IL-39) and diabetic neuropathy (IL-39). BMI was positively correlated with IL-39 (correlation coefficient [rs ]=0.27; p= .005) and glycosylated haemoglobin (rs = 0.31; p= .001), and negatively correlated with age at onset (rs = -0.24; p= .015). IL-37 and IL-39 levels were elevated in the serum of T2DM patients. Besides, IL-39 is proposed to be a novel cytokine associated with T2DM and positively correlated with BMI.