Abstract: Objective To explore the correlation of homocysteine with diabetic microangiopathy and the change after drug intervention. Methods A total of 200 patients with type 2 diabetes were selected between January and December 2013. The patients were divide into group of no microvascular disease and group of microvascular lesion according to the complications. Blood lipid, blood glucose, renal function and serum homocysteine were deteced pre-treatment and after 6 months treatment. A total of 100 cases of healthy subjects with physical examination over the same period were selected as control group according to the principle of age and gender matching. Results SBP, DBP, TG, TC, LDL, FBG, 2 hPBG, HbA1, SUN, SCr and HCY in group of no microvascular disease and group of microvascular lesion were significantly higher than that in control group（P<0.01）, while HDL were significantly lower（P<0.01）; SBP、DBP、SUN、SCr and HCY in group of microvascular lesion were significantly higher than that in group of no microvascular disease（P<0.01）; Multi factor Logistic regression analysis showed blood pressure, urea nitrogen, serum creatinine and homocysteine levels are risk factors for microvascular complications in patients with diabetes mellitus; HCY after treatment were significantly lower than that before treatment in group of no microvascular disease and group of microvascular lesion than（P<0.01）. Conclusion High homocysteine levels are risk factor of diabetic microvascular disease, and the homocysteine levels can be reduced after treatment.