This study investigated the value of Thiol/Disulfide homeostasis and ischemia-modified albumin (IMA) levels in discriminating diabetic cases with different stages of retinopathy and without retinopathy. In total, 122 patients with type 2 diabetes mellitus (DM) were enrolled in this prospective cross-sectional study. These patients were separated into three subgroups: Group 1 included 42 patients with DM and no diabetic retinopathy (DR), Group 2 included 40 patients with DM having non-proliferative DR and the Group 3 had 40 patients with DM having proliferative DR. The native thiol, total thiol, and disulfide levels and disulfide-native thiol, disulfide-total thiol, and native thiol-total thiol ratios as well as the IMA levels were analyzed and compared among the groups. There were no statistically significant differences regarding the ages and genders of the patients between the groups. The native thiol level, the total thiol level and the native thiol-total thiol ratio showed a statistically significantly reduction, while the disulfide level, the disulfide-native thiol ratio, and the disulfide-total thiol ratio showed a statistically significantly elevation in the Group 3 compared with the Group 1 and Group 2. Additionally, the mean IMA levels were statistically significantly higher in Group 3 when compared to Group 1 and Group 2 (p=.003 and p=.014, respectively). In conclusion, both Thiol/Disulfide homeostasis parameters and IMA levels increase with the progression of DR. Thiol/Disuldife homeostasis balance and IMA levels may be used a biomarker to monitor the tissue ischemia in DM and to discriminate the different stages of DR, in the future.