Background Diabetic retinopathy (DR) is a micro-vascular consequence of diabetes mellitus (DM) that manifests clinically as retinal ischemia, neovascularization, altered retinal permeability, and macular edema. In the adult population, DR is now considered a leading cause of blindness. Fetuin-A is a multifunctional glycoprotein that, because of its dual role in insulin resistance and angiogenesis, could be an early trigger of DR pathogenesis. Objective This study aimed to evaluate the level of Fetuin-A in diabetic patients with and without retinopathy and demonstrate if it could be used as an early indicator of DR. Patients and methods A case–control study enrolled 45 participants selected from Al-Zahraa University Hospital, between March 2021 and October 2021, they were divided into three groups: Group 1: healthy control group (n=15); Group 2: type 2 diabetic patients without DR (n=15); and Group 3: type 2 diabetic patients with DR (n=15). All groups were age- and sex-matched and were investigated by enzyme-linked immunosorbent assay (ELISA) to evaluate serum level of Fetuin-A. Results There was a highly significant difference of FBG, 2HPP, and HbA1c between the studied groups (p< 0.001), while there was no significant difference between the three studied groups regarding Fetuin-A. There were no significant correlation between Fetuin-A, glycemic parameters, and diabetic duration in Groups 2 and 3. Conclusion Fetuin-A has no significant role in the pathogenesis of diabetic retinopathy.