Abstract: Objective To investigate the relationship between CD4⁺CD28^null T cell and diabetic microangiopathy. Methods One hundred and forty-one patients with type 2 diabetes were selected in the endocrinology department.According to the presence of microvascular disease,these patients were divided into four groups:the type 2 diabetes patients without documented microangiopathy(T2DM) group;the diabetic retinopathy(DR) group;the diabetic nephropathy(DN) group;the group with diabetic retinopathy and nephropathy(DR+DN) group.The healthy control group was consisted of 26 subjects.The expression of CD4⁺CD28^null T cells of these groups were compared and analyzed to find out the related factors which affects diabetic microangiopathy. Results Compared with normal control group,the expression of CD4⁺CD28^null T cell of all diabetic groups are significantly increased(χ²=19.98,P＜0.01).Compared with T2DM group,the expression of CD4⁺CD28^null T cell of groups DR,DN and DR+DN are significantly increased(Z=-2.19,-2.87,-2.67,P＜0.05),and CRP of these groups are also significantly increased(Z=-3.11,-2.36,-2.86,P＜0.05).But the differences of the expression of CD4⁺CD28^null T cell and CRP between groups DR,DN and DR+DN have no statistical significance.The logistic regression analysis shows that the duration,the expression of CD4⁺CD28^null T cell,CRP and waistline are the independent risk factors for diabetic microangiopathy. Conclusion The expression of CD4⁺CD28^null T cell of type 2 diabetes patients is higher than that of the healthy subjects.Further,these diabetes patients with microangiopathy have a higher expression.CD4⁺CD28^null T cell may affect the progress of diabetic microangiopathy independently.