Diabetic　retinopathy　(DR)　is　one　of　the　most　common　microvascular　complications　of　diabetes　mellitus　and　is　considered　as　a　leading　cause　of　blindness.　Oxidative　stress　and　inflammation　are　significant　drivers　for　the　development　of　DR.　Eriodictyol,　a　flavonoid　compound,　was　proved　to　possess　anti-inflammatory,　antioxidative,　and　antidiabetic　activities.　However,　the　role　of　eriodictyol　in　DR　has　not　been　unveiled.　In　the　current　study,　we　explored　the　protective　effects　of　eriodictyol　on　high　glucose　(HG)-induced　rat　retinal　ganglial　cells　(RGCs).　The　results　suggested　that　eriodictyol　improved　cell　viability　of　HG-induced　rat　RGC-5　cells　in　a　dose-dependent　manner.　Eriodictyol　reduced　the　reactive　oxygen　species　production　and　increased　the　activities　of　superoxide　dismutase,　glutathione　peroxidase　and　catalase　in　rat　RGC-5　cells　in　response　to　HG　stimulation.　The　production　of　proinflammatory　cytokines　including　tumor　necrosis　factor　alpha　and　interleukin-8　was　diminished　after　eriodictyol　treatment.　Eriodictyol　also　suppressed　cell　apoptosis　induced　HG　in　rat　RGC-5　cells.　Furthermore,　eriodictyol　enhanced　the　nuclear　translocation　of　nuclear　factor　erythroid-2 (E2)-related　factor　2　(Nrf2)　and　elevated　the　expression　of　antioxidant　enzyme　heme-oxygenase-1　(HO-1).　These　findings　suggested　that　eriodictyol　protects　the　RGC-5　cells　from　HG-induced　oxidative　stress,　inflammation,　and　cell　apoptosis　through　regulating　the　activation　of　Nrf2/HO-1　pathway.