Diabetic retinopathy (DR) is a serious consequence of diabetes that is caused by reactive oxygen species (ROS) generated under conditions of oxidative stress. The nuclear factor erythroid‑2‑related factor 2 (NFE2L2) plays a critical endogenous protective role against oxidative stress, as it controls the expression of superoxide dismutase (SOD) and heme oxygenase‑1 (HO‑1) genes. The aim of the present study was to determine the gene expression level of NFE2L2 and its association with SOD and HO‑1 serum levels among patients with type 2 diabetes and retinopathy. The present study included 90 patients diagnosed with type 2 diabetes mellitus (48 females and 42 males), aged 40 to 80 years. The patients were divided into two groups as follows: Group A included 60 patients diagnosed with diabetic retinopathy (DR) [among them were 29 patients with non‑proliferative DR (NPDR) and 31 patients with proliferative DR (PDR)] and group B included 30 diabetic patients without any evidence of DR (DWR), considered as the control group to be enrolled in the study. The results revealed significantly lower serum levels of SOD and HO‑1 among the patients with PDR and NPDR, compared with the patients in the DWR group. However, no significant differences were noted between the PDR and NPDR groups as regards the SOD and HO‑1 levels. Of note, the gene expression of NFE2L2 was 3‑fold higher in the DR groups compared with the DWR group. The gene expression of NFE2L2 also exhibited a significant negative correlation with the serum SOD and HO‑1 levels in the DR groups. Furthermore, the decline in SOD and HO‑1 activity in the DR groups indicated the consumption of antioxidant capacity for detoxifying ROS due to uncontrolled hyperglycemia, thus, increasing the expression of NFE2L2 to counteract the oxidative stress in DR. On the whole, the present study demonstrates that NFE2L2 expression may be a good indicator of the progression of DR.

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