Type 2 diabetes mellitus (T2DM) is a major public health problem in China. Diagnostic markers are urgently needed to identify individuals at risk of developing T2DM and thus encouraging healthier life styles. Circulating miRNAs are valuable sources for non-invasive biomarkers of various diseases. The aim of this study was to examine whether reduced miR-126 expression could predict the onset of T2DM in susceptible individuals. Two groups of study subjects were involved, one group was diagnosed T2DM in 2013 and the other group was healthy control. To this end, our results showed that miR-126 expression were already decreased before the manifestation of T2DM. Univariable logistic regression confirmed that the plasma miR-126 level was inversely associated with the onset of DM (P = 0.0158 < 0.05), suggesting reduced miR-126 is a predictor for the onset of T2DM. According to the logistic regression model and ROC curve, a cut-off points of miR-126 plasma level as 35 is recommended for clinical study to predict whether an individual is more likely to develop T2DM. If miR-126 expression is lower than 35, the individual is more likely to T2DM in the next 2 years. In conclusion, our results support the notion that the circulating miR-126 can be developed into a non-invasive and rapid diagnostic tool for the prediction of susceptible individuals to developing T2DM. (C) 2015 Elsevier Inc. All rights reserved.