AIM: To investigate the effects of vialinin A on viability of human retinal endothelial cells (HRECs) under high glucose condition and its potential mechanism. METHODS: The HRECs were divided into four groups: normal glucose control group (NG, 5 mmol/L D-glucose), high glucose group (HG, 30 mmol/L D-glucose), HG+1 μmol/L vialinin A group, and HG+5 μmol/L vialinin A group. The cell viabilities were measured with cell counting kit-8 (CCK-8) assay for proliferation, with scratch assay for migration, and tube formation, for evaluation of the impact of vialinin A on cellular behaviour. Real-time PCR and Western blotting were used to determine the expression level of vascular endothelial growth factor (VEGF). RESULTS: The proliferative capacity and migration of HRECs was reduced by 5 μmol/L vialinin A in high glucose environment (both P<0.05). Vialinin A also inhibited high-glucose-induced tube formation of HRECs. The expression level of VEGF and PI3K in HRECs was also significantly decreased by vialinin A (P<0.05). CONCLUSION: Vialinin A inhibits the cell viability of HRECs. It may serve as a potential target for anti-angiogenic therapy.