Hyperglycemia triggers metabolic and inflammatory responses, which lead to vascular inflammation and consequently induce microvascular and/or macrovascular diabetic complications. 5-bromo-3,4-dihydroxybenzaldehyde (BDB), a marine red algae-derived bromophenol compound, is found to have diverse bioactivities, including the effect of anti-inflammation and anti-diabetes, though the mechanism of which is still unclear. To evaluate the anti-vasculopathy of BDB and explore the possible mechanism involved. Firstly, MTT assay was used to optimize the treatment concentration of glucose and BDB with HUVECs. Subsequently, we adopted two concentrations of BDB (50 µM and 100 µM) to verify the protective effect of BDB on vascular model, which was established by HUVECs from high glucose (30 mM)-induced damage. The cell migration and tube formation were used to evaluate the function of HUVECS. Moreover, the related mechanisms were analyzed by assays for flow cytometry, ELISA, qPCR, intracellular ROS and western blot. The present study demonstrated that BDB could protect endothelial cells from apoptosis caused by high glucose treatment. BDB also significantly reduced the secretion of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, induced by high glucose, which was also in agreement to the decrease of p65 protein expression and activities of NF-ĸB regulated by BDB. The reactive oxygen species (ROS) production and phosphorylation of 38 protein expression were also down-regulated by BDB compared to high glucose alone treatment. Furthermore, BDB reserved the endothelial cells functions of migration and tube formation under high glucose condition, which suggested that BDB could be a potential candidate in treating vascular inflammation induced by hyperglycemia.