〔Abstract〕 Objective To investigate the changes and clinical significance of interleukin-22(IL-22) and interleukin-22 binding protein(IL-22 BP) in peripheral blood of patients with type 2 diabetes mellitus(T2 DM). Methods A total of 90 patients with T2 DM were selected as the research objects of type 2 diabetes group, and another 40 normal healthy people were selected as the control group. The levels of IL-22 and IL-22 BP were measured by enzyme-linked immunosorbent assay(ELISA), and biochemical indexes and chronic complications were recorded. Results Compared with the normal control group, the level of IL-22 expression in T2 DM group was lower(P<0.001), while the level of IL-22 BP was higher(P<0.01). Correlation analysis showed that IL-22 was negatively correlated with IL-22 BP and ankle brachial index(ABI)(ρ=-0.273,-0.312,P<0.01), positively correlated with waist hip ratio(WHR), fasting plasma glucose(FPG), glycosylated hemoglobin(HbA1 C) and homeostasic model assessment of insulin resistance(HOMA-IR)(ρ=0.209, 0.282, 0.243, 0.241,P<0.05), IL-22 BP was negatively correlated with HbA1 C and low density lipoprotein cholesterol(LDL-C) to different degrees(ρ=-0.290,-0.208,P<0.05). Logistic regression analysis showed that IL-22 and IL-22 BP levels were related factors for the pathogenesis of T2 DM. Compared with non-diabetic nephropathy group, the expression of IL-22 in diabetic nephropathy group decreased(P<0.01), while the expression of IL-22 BP increased(P<0.05). Conclusion The level of IL-22 expression decreases and IL-22 BP expression increases in type 2 diabetic patients, which may be related to blood glucose control, T2 DM and diabetic nephropathy.