The purpose of this study was to verify that acid polysaccharides from Buddleja officinalis Maxim (APBOM) could relieve diabetic retinopathy (DR) through inhibition of angiogenesis via activation of the Nrf2/ARE signaling pathway. Transgenic db/db mice were used to establish a DR model, and it was found that APBOM could improve levels of blood glucose, blood lipids and insulin, and further improve pathological retinal tissue structure as well as vascular network structure. Moreover, APBOM could lessen the amount of angiogenesis by reducing the expression of CD34 and VEGF, and then delay the development process of DR. In in vitro mechanistic experiments, the generation of ROS was inhibited after APBOM intervention, and the expression of CD34, CD31 and VEGF was decreased. Furthermore, the mRNA and protein levels of HO-1, NQO1, SOD and Nrf2 were increased, which indicated that APBOM might promote expression of the Nrf2/ARE signaling pathway. Overall, APBOM might alleviate DR by inhibiting angiogenesis and activating the Nrf2/ARE signaling pathway.