Diabetic cardiovascular diseases are leading causes of death. In diabetic patients, oxidative stress is key event in cardiovascular disease (CVD) development. Uncoupling protein 2 (UCP2) and myeloperoxidase (MPO) were identified as molecules regulating oxidative stress effects of oxygen free radicals. This work aimed to evaluate association of UCP2-866G/A (rs659366) gene polymorphism and serum MPO with CVD among type 2 diabetic patients. The present work was conducted on 80 type 2 diabetic Egyptian patients including 40 patients with CVD compared to 40 age- and sex-matched non-CVD patients; recruited from Outpatient Clinics in Beni-suef University Hospital and Kasr Eleiny Hospital. Lipid profile was assayed. Serum MPO was analyzed using enzyme-linked immunosorbent assay. UCP2-866G/A (rs659366) gene polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism. Statistically significant increase in concentration of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) was found among CVD patients with MPO ˃ 44.3 ng/ml (P=0.01 and 0.019, respectively). Serum MPO showed significant positive correlation with TC and LDL-C (P=0.004 and 0.002, respectively). The UCP2-866 (rs659366) (GA and AA) genotype variants did not demonstrate statistically significant higher risk to develop cardiovascular events, yet were observed to have higher frequency among CVD patients and among patients with MPO ˃ 44.3ng/ml. In conclusion, our results revealed significant correlation between serum myeloperoxidase and CVD lipid risk factors in diabetic patients. This study suggests UCP2 -866G/A (rs659366) gene polymorphism and MPO as target assay studies on CVD etiology and oxidative stress parameters evaluation among type 2 diabetic patients.