Purpose: To investigate the relationship of serum levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) with diabetic retinopathy (DRP) grade and treatment modality in patients with diabetes mellitus. Material and Methods:. One hundred twenty four patients with type II diabetes mellitus and 20 age and sex matched healthy subjects were enrolled in the study. The diabetic patients were divided into two groups as patients who are receiving oral anti-diabetic (OAD) drugs or patients who are receiving insulin treatment. Both groups were also divided into four subgroups according to stage of retinopathy as following: 1. no retinopathy, 2. background DRP, 3. preproliferative DRP, 4. proliferative DRP and 5. control group. In all groups, body mass index was calculated, fasting serum VEGF and NO levels were measured and mean values between groups were statistically evaluated. Blood pressure, serum C peptide, albumin, HDL, LDL, cholesterol, creatinin, HbAl c, vitamin B 12, folic acid, fibrinogen and ESR were measured in all patients. Results: There were no statistically significant differences between groups as age, body mass index, systolic and diastolic blood pressure, C peptide, albumin, and HDL, LDL, total cholesterol levels. There was no statistically significant difference in serum VEGF and NO between retinopathy groups. VEGF levels were found to be significantly higher in proliferative DRP group compared to control group (p:0.014). NO levels was found to be higher in all diabetic groups compared to control group (p:0.034, 0.003, 0.016 and 0.001). NO was found to be higher in patients with background DRP in the OAD group compared to insulin group, while there was no difference between two treatment modality in all groups for VEGF levels. Conclusion: Serum levels of VEGF and NO were significantly higher in proliferative retinopathy compared to control group. It was suggested that these parameters can be used as a peripheral marker of proliferative DRP, and may be useful for biochemical follow-up of progression and regression of proliferative process.