Objective To study the effect of hyperglycemia on uncoupling protein (UCP) mRNA expression in mouse brain microvessel endothelial cell line bEnd.3, and to investigate the regulatory effect of resveratrol on the expression.Methods Mouse bEnd.3 cells were cultured in vitro.The mRNA levels of UCP1-5 in bEnd.3 cells were determined by RT-PCR after exposure to different concentrations of glucose(5.5、25 mmol/L) and resveratrol (25 μmol/L).Results We found that exposure to 25 mmol/L glucose for 24 h up-regulated the expression of UCP4 and UCP5 mRNA levels (P<0.05), but had no noticeable influence on the expression of UCP1 and UCP2 mRNA levels. Resveratrol increased UCP5 mRNA levels under baseline and hyperglycemia conditions (P<0.05), and it decreased reactive oxygen specices(ROS) induced by hyperglycemia condition (P<0.05).Conclusion High glucose stimulation can specifically up-regulate UCP4 and UCP5 mRNA expression in mouse brain microvessel endothelial cells. Resveratrol can greatly decrease ROS production induced by hyperglycemia condition and up-regulate UCP5 mRNA expression.