We illuminated that the molecular signal transduction underlying the TGF-β1-mediated protective effect is associated with its promotion of expression of Nrf2, Keap1, HIF-1α, ALDH3A1, and HO-1 proteins, suggesting that TGF-β1 may act as a potential initiator for retinal protection in diabetic retinopathy. Here, NFE2L2 is linked to diabetic retinopathy.