Cortistatin (CST) is a recently discovered cyclic neuropeptide with multiple bioactive effects. The aim of this study was to investigate the relationship between plasma CST and various metabolic markers in patients with newly diagnosed type 2 diabetes mellitus (T2DM). For this study, 60 patients with newly diagnosed T2DM and 38 age- and gender-matched healthy controls were recruited. Fasting plasma glucose (FPG), serum insulin and hemoglobin A1c (HbA1c) levels and a blood lipid profile were obtained with commercially available diagnostic reagents. CST plasma levels were determined using an enzyme immunoassay kit. The results showed that the plasma levels of CST were substantially lower in patients with newly diagnosed T2DM compared with the healthy controls. Plasma CST levels were positively correlated with high-density lipoprotein and negatively related to FPG, serum insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) and HbA1c in all subjects. Further analysis showed that CST levels were positively correlated with systolic blood pressure and negatively correlated with FPG, serum insulin, HOMA-IR and HbA1c in patients with newly diagnosed T2DM. Moreover, logistic regression analyses indicated that plasma CST was correlated with newly diagnosed T2DM. In conclusion, patients with newly diagnosed T2DM had significantly lower plasma levels of CST than healthy controls, and plasma CST was associated with glucose metabolism and insulin resistance, indicating a potential role of CST in the development of T2DM.