We investigated the inhibitory effect of sitagliptin on albuminuria in patients with type 2 diabetes. Thirty-six patients (19 men and 17 women) whose HbA1c was higher than 6.5% (NGSP) despite receiving education on diet and exercise and medical treatment for at least 6 months at our clinic were enrolled into this study and were successfully followed over 6 months of sitagliptin treatment. Sitagliptin (50 mg/day) treatment significantly lowered both systolic and diastolic blood pressures, fasting blood glucose and postprandial blood glucose, HbA1c, and glycated albumin at 3 months and 6 months. Significant reductions in highly sensitive C-reactive protein and soluble vascular cell adhesion molecule 1 were also observed at 6 months. Urinary albumin excretion (measured as urinary albumin-to-creatinine ratio (ACR: mg/g Cr)) did not change in the 6 months before sitagliptin treatment (ΔACR: 2.3 ± 19.9) and decreased in the 6 months after sitagliptin treatment (ΔACR: -20.6 ± 24.6); these differences were statistically significant. At 6 months, the ACR decreased from 11.6 ± 8.4 to 4.5 ± 5.0 in 13 patients with normoalbuminuria (ACR < 30), from 98.4 ± 79 to 24.9 ± 20 in 15 patients with microalbuminuria (30 < ACR < 300), and from 1263 ± 492 to 561 ± 89 in 8 patients with macroalbuminuria (ACR > 300). Thus, the present findings strongly suggest that sitagliptin reduces albuminuria without lowering the estimated glomerular filtration rate, most likely depending on known factors such as blood sugar reduction, blood pressure reduction, and inflammation reduction, as well as yet undetermined factors caused by an increase in active glucagon-like peptide-1.