Diabetes mellitus is a chronic disease associated with significant morbidity and mortality owing to its multiple micro and macrovascular complications [
1,
2]. Diabetes mellitus has reached epidemic proportions with the greatest impact in low income countries where it remains underdiagnosed, under investigated, and undertreated [
3‐
5]. The epidemic rise in diabetes mellitus poses significant public health and socioeconomic challenges through diabetic complications affecting different organs with various impact. The eye is the most commonly affected organ in both type 1 and type 2 diabetes. [
6]. Diabetic retinopathy is the most serious and commonest ocular complication associated with T2DM and one of the leading causes of secondary blindness worldwide [
3]. Its prevalence has been reported to range from 15.3% to 42.4% in different studies [
1]. Diabetic retinopathy is a disease characterized by microvascular alterations progressively leading to retinal ischemia, retinal hyper-permeability, retinal neovascularization, and macular edema. If left untreated patients with diabetic retinopathy can suffer severe visual loss [
7]. In developed countries, diabetic retinopathy constitutes the leading cause of blindness in the working age population [
8]. Different risk and progression factors for diabetic retinopathy have been documented and classified as modifiable risk factors (blood glucose, blood pressure, serum lipids, and smoking) and non-modifiable risk factors (duration, age, genetic predisposition, and ethnicity) [
9]. However, recent literature has clearly demonstrated an incremented risk of diabetic retinopathy with regard to insulin treatment [
1,
10‐
12]. Nevertheless, the mechanism underlying this paradoxical association is not well understood. Here we revisit evidence on the association between diabetic retinopathy and insulin use, and we propose a novel hypothesis to support this relationship.