Background <p>Diabetic retinopathy (DR) remains a major cause of preventable vision loss worldwide and arises from the convergence of chronic inflammation, oxidative injury, and metabolic dysregulation that ultimately compromises vascular and neuronal integrity of the retina. Although intravitreal anti-VEGF agents have improved the management of DR, significant limitations such as incomplete therapeutic response, repeated administration and high cost underscore the need for alternative or adjunctive strategies.</p> Main body <p>Emerging preclinical evidence suggests that dysregulated signaling via the epidermal growth factor receptor (EGFR) plays a critical role in DR pathogenesis. EGFR and some of its ligands are expressed across multiple retinal cell types and play important roles in normal development and in regulating homeostasis in adult retinas. However, in hyperglycemia/diabetes enhanced EGFR signaling promotes vascular hyperpermeability, pericyte loss, glial reactivity, inflammatory amplification, and pro-fibrotic remodeling that contributes to both early microvascular dysfunction and later proliferative changes in experimental models. Several preclinical studies indicate that pharmacologic blockade of EGFR or downstream signaling pathways attenuates angiogenesis, inflammation, and gliosis in models of DR.</p> Conclusions <p>These emerging preclinical findings implicate EGFR as a promising therapeutic target to complement or extend beyond VEGF-centered approaches. Further validation of the role of EGFR and its ligands in mediating retinal pathology in clinically relevant models will be essential for advancing EGFR-targeted interventions toward clinical translation.</p>