AIM: To observe the expression of proline hydroxylase domain 2 (PHD2) in the retina of diabetic rats and investigate the relationship between PHD2 and relevant intraocular vascular proliferation factors. METHODS: Sixty male specific pathogen free (SPF) Sprague-Dawley (SD) rats were randomly divided into two groups: the diabetic group and the control group. The rats in the diabetic group were intraperitoneally injected with 60 mg/kg (0.60 mL/100g) of streptozotocin to induce a diabetic rat model. The rats in the control group were injected with an equal volume of sodium citrate buffer solution by the same method. Hematoxylin-eosin (HE) staining and immumofluorescence (IF) method were adopted to observe the pathological changes of retinal tissues and the expression of PHD2, glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF) by 8wk. RT-PCR method was applied to detect the expressions of mRNA of PHD2, VEGF and GFAP. The relationship between PHD2 and other vascular proliferation factors was analyzed. RESULTS: HE staining showed that there was the retinal tissue edema in the diabetic group, and the arrangement was in disorder, and proliferation could be seen. IF staining: in the retina of normal rats, PHD2 was not expressed, GFAP and VEGF were mainly expressed in astrocytes; while in the diabetic rats, PHD2, GFAP and VEGF staining showed strong positivity in all retinal layers, mainly in neurogliocytes. PHD2 was co-expressed with VEGF and GFAP. The mRNA expression levels of PHD2, GFAP and VEGF in the diabetic group were obviously higher than that in the control group,respectively 1.83 times, 1.75 times and 2.08 times. The difference had statistical significance (P<0.01). CONCLUSION: The high expression of PHD2 in the retina of early-stage diabetic rats might result from secretion of neurogliocytes induced by local high-concentration blood glucose, thus promoting the expression of VEGF and GFAP. PHD2 plays an important role during the occurrence of diabetic retinopathy.