Objective To observe the influence of dipeptidyl peptidase-4 (DPP-4) inhibitors on β2- microglobulin (β2-MG) in patients with early diabetic chronic kidney disease (CKD). Methods In this study, 72 patients with early CKD (CKD group), 80 diabetic patients with normal urine albumin (DM group) and 80 normal healthy persons (NC group) were selected. The clinical data and biochemical parameters were collected and compared among the three groups. Then the CKD group was divided into a conventional subgroup and a DPP-4 subgroup with 36 in each subgroup; both subgroups adopted the diabetic diet, exercise programs, on the base of control of their blood glucose, lipids and blood pressure; the patients in the DPP-4 subgroup were treated with DPP-4 inhibitors 5 mg per day for 12 weeks. The biochemical indicators and inflammatory factors were compared between the two subgroups before and after treatment. The factors influencing β2-MG were analyzed by multivariate linear regression analysis. Results The levels of BMI, FPG, 2-h PG, HbA1c, 24-h UAlb, IL-6, TNF-α and β2-MG in the CKD group and the DM group were higher than those in the NC group (P < 0.05); and the levels of 2-h PG, 24-h UAlb, IL-6, TNF-α and β2-MG in the CKD group were higher than those in the DM group (P < 0.05). In both CKD subgroups, the levels of FPG, 2-h PG, HbA1c and 24-h UAlb were reduced after treatment compared to the pre-treatment levels (P < 0.05); after treatment the FPG, 2-h PG, HbA1c and 24-h UAlb levels in the DPP-4 subgroup were lower than those in the conventional subgroup (P < 0.05). Compared with pre-treatment values, the post-treatment levels of IL-6, TNF-α and β2-MG were reduced in both CKD subgroups (P < 0.05); after treatment the levels of IL-6, TNF-α and β2-MG in the DPP-4 subgroup were lower than those in the conventional subgroup (P < 0.05). β2-MG level was positively correlated with DM course, BMI, 2-h PG, HbA1c, 24-h UAlb, IL-6 and TNF-α levels (P < 0.05). DM course and HbA1c were the influencing factors for β2-MG in the patients with early CKD (P < 0.05). Conclusions DPP-4 inhibitors can effectively reduce blood glucose level in the patients with early CKD, and lower β2-MG level, eliminate or control pro-inflammatory factors, reduce the damage of renal tubules, and therefore delay the development of CKD.