Objective To investigate the expression and prolyl hydroxylase (PHD)2 in retina of diabetic rats.Methods Wistar rats were randomly divided into the control group (n=48) and the diabetes group (n=60). The rats in diabetes group were induced with streptozotocin (STZ) injection creating a diabetic retinopathy model. The same volume of citric acid buffer was injected into the rats in the control group. Fluorescence microscope was used to observe the retinal vasculature at one, three and six months after injection. Evans blue perfusion was used to detect the bloodretinal barrier (BRB) permeability. Immunohistochemical staining was used to observe the distribution of PHD-2 positive staining. Western blot was used to measure the protein expression of PHD-2, hypoxia inducible factor(HIF)-1alpha; and vascular endothelial growth factor (VEGF) every month from one to six months after injection. Results The vascularization was normal and form was clear in retina of rats in control group. The retinal blood vessels of rats in diabetes group showed significantly increased fluorescence. Compared with the control group, the BRB permeability was significantly increased in diabetes group (P<0.05). Abundant expression of PHD-2 protein was detected in the inner layers of retina in control and diabetes group.Compared with the control group, the PHD-2 expression was decreased in diabetes group at one and two months after injection (t=16.230, 16.390;P<0.05). The HIF-1alpha; expression was significantly increased in diabetes group at one, two and three months after injection (t=27.073, 36.709, 10.176; P<0.05). The VEGF expression was significantly increased in diabetes group every month from one to six months after injection (t=13.547, 31.984, 21.897, 8.912, 9.019, 14.046; P<0.05). Conclusions There is abundant expression of PHD-2 in the inner layer of retina in diabetic rats. PHD-2 may play an important role in diabetic retinopathy, which is correlated with VEGF.