Aim To clarify the molecular mechanism of protective effect of rosiglitazone on vascular complication of diabetes. Methods Human umbilical vascular endothelial cells (HUVEC) were exposed to medium or high glucose in the presence or absence of different doses of rosiglitazone. Nuclear translocation of nuclear factor-κB(NF-κB) was measured using the electrophoretic mobility shift assay and immunofluorescence. Expression of vascular cell adhesion molecule-1(VCAM-1) was determined by immunofluorescence. Results 25 mmol/L D-glucose significantly induced nuclear translocation of NF-κB in HUVEC (P><0.001 vs that of basal level),which was prevented by 5 and 25 μmol/L of rosiglitazone in a dose-dependent manner. The suppression rate was 25.17% (P>=0.001) and 51.79% (P><0.001). Rosiglitazone also prevented the increased expression of VCAM-1 induced by D-glucose. Conclusion Rosiglitazone directly protects vascular function via inhibition of inflammation in vascular endothelial cells and that is perhaps one of the mechanisms of rosiglitazone improving vascular complication of diabetes.