【Objective】 To evaluate the efficacy of Sitagliptin or Glimepiride on glucose fluctuations and changes in blood inflammatory and oxidative stress markers for the patients of type 2 diabetes mellitus with inadequate glycemic control by Metformin monotherapy. 【Methods】 A total of 46 patients with type 2 diabetes mellitus were randomized to receive Sitagliptin (S group) or Glimepiride (G group) for 12 weeks. HbA1c, FBG, 2-h PG, glucose fluctuations, 3-NT, CRP and safety after treatment were assessed in both groups and compared between the groups. 【Results】 The levels of HbA1c, FBG and 2-h PG after treatment were remarkably decreased in both groups (P < 0.05), and were not different between the groups (P > 0.05). The glucose fluctuations and 3-NT level were significantly reduced in both groups after therapy (P < 0.05), and they were lower in the S group than in the G group (P < 0.05). The level of CRP was markedly lowered only in the S group after therapy (P < 0.05). The BMI and incidence of total adverse reactions in the S group were lower than those in the G group (P < 0.05). 【Conclusions】 The efficacy of Metformin combined with Sitagliptin on glucose fluctuations, changes in blood inflammatory and oxidative stress markers and safety is superior to the efficacy of Metformin combined with Glimepiride.