AIM: To investigate the effect of ginsenoside-Rg3 on the expression of vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) in retina with diabetic rats and its roles in preventing neovascularization in diabetes. METHODS: Sixty male Wistar rats were divided into 3 groups randomly: negative control group, diabetic control group and ginsenoside-Rg3 treatment group (5mg/kg, 0.2mg/mL) followed by establishing diabetic model. The expression of VEGF and TNF-α were measured after 8 weeks. RESULTS: There were significant differences among negative control group, diabetic control group and ginsenoside-Rg3 treatment group in the expression of VEGF and TNF-α (F =129.363, 211.992; all the P <0.01). VEGF and TNF-α expression were significantly higher in diabetic control group and ginsenoside-Rg3 treatment group than that in negative control group (P <0.01), with a significant reduction in ginsenoside-Rg3 treatment group than that in diabetic control group (P <0.01). CONCLUSION: Ginsenoside-Rg3 can down-regulate the expression of VEGF and TNF-α in retina, which may interfere in the development of diabetic retinopathy.