Objective To observe the effect of sitagliptin on carotid intima-media thickness (c-IMT) and serum hs-CRP and IL-6 levels in the patients with newly diagnosed type 2 diabetes mellitus. Methods 65 patients with newly diagnosed type 2 diabetes mellitus who were admitted to the outpatient clinic and were hospitalized in our hospital were selected. They were randomly divided into sitagliptin phosphate tablet group (experimental group) with 35 cases and metformin hydrochloride tablet group (control group) with 30 cases. All patients were given health education about diabetes, diet guidance and exercise. All patients were given drawing of venous blood at a fasting condition ≥10 h before treatment and 6 months after treatment to determine the following indicators: FPG, 2 hPG, hs-CRP, IL-6, TC, TG, HDL-c, LDL-c, HbA1 c, hs-CRP, IL-6, etc, and c-IMT was determined. Results There was no statistically significant difference in blood glucose, blood lipids, inflammation index and c-IMT between the two groups before treatment (P>0.05); after treatment, FPG, 2 hPG and HbA1 c were significantly lower than those before treatment in both groups, and the difference was statistically significant (P<0.01). There were statistically significant differences in FPG and HbA1 c between the two groups (P<0.01). There was no statistically significant difference in 2-hour postprandial blood glucose between groups (P>0.05). The c-IMT, hs-CRP and IL-6 levels in the experimental group after treatment were significantly lower than those before treatment, and the differences were statistically significant (P<0.05). There was no significant change in c-IMT in control group after treatment (P>0.05). hs-CRP and IL-6 had a decreasing trend compared with those before treatment, and the difference was not statistically significant (P>0.05). There were statistically significant differences in c-IMT, hs-CRP and IL-6 between the two groups after treatment (P<0.05). Spearman linear correlation analysis: c-IMT was positively correlated with hs-CRP levels and IL-6 (r=0.6585, P=0.000; r=0.571, P=0.000). There was no significant correlation between fasting blood glucose and glycosylated hemoglobin (P>0.05). Conclusion The DPP-4 inhibitor of sitagliptin has a clear hypoglycemic effect and can reduce c-IMT, hs-CRP and IL-6. The anti-inflammatory effects besides hypoglycemic effect may be involved in the reduction of atherosclerosis in the patients with diabetes mellitus.