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The aim of this study was to investigate the role of miR-21 in inflammatory responses in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic (T2D) and healthy subjects. 20 healthy and 20 T2D subjects were enrolled in the study. miR-21 expression in PBMCs of the subjects was measured using real-time PCR. IL-6 and TNF-α levels in culture supernatants were quantified using ELISA. miR-21 expression was not significantly different between the diabetic and nondiabetic groups. A downregulation of miR-21 expression was observed in PBMCs of obese subjects in both diabetic and nondiabetic groups. In addition, miR-21 expression was negatively correlated with weight, waist circumference, body mass index, and triglyceride in both the diabetic and nondiabetic groups. Our results also demonstrated that the PBMCs of obese subjects significantly secreted a higher level of IL-6 and TNF-α in comparison with the PBMCs of nonobese subjects. Furthermore, a significant inverse correlation between miR-21 expression and TNF-α and IL-6 production from the PBMCs was observed. These data suggest that miR-21 expression is decreased in PBMCs of obese subjects and reduced expression appears to be associated with increased secreted cytokine level in media of PBMCs of obese subjects.