Background: In recent years, numerous studies have addressed the role of other factors, especially the immune system, on developing diabetic retinopathy. Given the role of interferons in regulating immune system activities, the present study was conducted to investigate serum levels of interferon-gamma in patients with diabetic retinopathy. Materials and Methods: The present research was conducted on 42 patients with type 2 diabetes and diabetic retinopathy in the case group and 41 patients with only type 2 diabetes in the control group. The two groups were matched in terms of age and gender. In the previous three months, the participants had not developed severe bacterial, viral or parasitic infections, not undergone ocular and non-ocular surgeries and not taken immunosuppressants. After measuring the patients’ systolic and diastolic blood pressures, their urine and blood samples were collected for the laboratory analysis of CBC, LDL, HDL, TG, total cholesterol, proteinuria, FBS, HbA1c, ESR, CRP, BUN, Creatinine and interferon gamma. The data collected were statistically analyzed in SPSS-18. Results: Out of 83 patients aged 41-78 years with type 2 diabetes, 42 patients were assigned to the case group and 41 to the control group. The mean of age of the case group was 59. 69± 6. 866 years and that of the controls 58. 71± 7. 410. Based on statistical methods, the two groups were matched in terms of age and gender. Although serum levels of interferon gamma were higher in the case group compared to in the controls, the difference was statistically insignificant (P>0. 05). No significant differences were also observed between the two groups in terms of WBC, LDL, total cholesterol, FBS, CRP, Creatinine, HDL and diastolic blood pressure (P>0. 05). According to the logistic regression model, the risk of developing retinopathy was approximately 8 times higher in the insulin users compared to in those using oral medicines. Conclusion: The statistical analysis and regression model did not suggest significant relationships between serum levels of interferon gamma and diabetic retinopathy. The two groups were significantly different in terms of insulin consumption. Further studies are recommended to be conducted to find the role of immunological factors in developing diabetic retinopathy.