In this study, we investigated the protective effect of long-term hyperglycemia control through treatment with pioglitazone (PGZ), a synthetic ligand of peroxisome proliferator-activated receptor-γ (PPAR-γ), on retinal tissues after AION inducement in mice fed a high-fat diet (HFD) with streptozotocin (STZ)-induced diabetes. Here, PPARG is linked to diabetes mellitus.