Studies have confirmed that endothelial progenitor cells (EPCs) are involved in diabetic complications. The present study assessed the action of the dipeptidyl peptidase-4 inhibitor sitagliptin on EPCs in newly diagnosed type 2 diabetes patients. 60 newly-diagnosed type 2 diabetes patients were randomly divided into three treatment groups: sitagliptin (n = 20), metformin (n = 20), and combination sitagliptin and metformin (n = 20). Patients were treated once daily for 3 days. Before and after each treatment, the number of EPCs and concentration of soluble mediators (glucagon-like peptide 1 (GLP-1), nitric oxide (NO), endothelin-1 (ET-1), and stromal cell-derived factor-1α (SDF-1α)) were determined. The number of CD34+KDR+ and CD34+CD133+KDR+ EPCs and concentration of GLP-1, NO, and SDF-1α in sitagliptin and combination groups were both increased (both p<0.05) but to a greater extent in the combination group (p<0.05). Pearson correlation analysis and multiple linear regression analyses showed that the change in EPC numbers correlated with changes in peripheral GLP-1, NO, and SDF-1α levels (p<0.05). Sitagliptin is able to directly increase the number of peripheral blood EPCs. This direct effect is to be important for lowering vascular risk in early diabetes before macrovascular complications appear.