Objective To determine the effect of pioglitazone on visfantin-induced inflammatory injury in human vascular endothelial cells and investigate the underlying signal pathway of pioglitazone in improving endothelial functions. Methods Human umbilical vein endothelial cells (HUVECs) were treated by different concentrations of visfantin. Then Western blotting was used to detect the expression of Toll-like receptor4 (TLR4), intercellular cell adhesion molecule-1 (ICAM-1), nuclear factor-κB (NF-κB) and inhibitor of NK- κB-α (IκB-α). Their expression levels were measured again after the cells were respectively exposed to the agonist of peroxisome proliferator activated receptor gamma (PPARγ), pioglitazone. Results Compared with the control group, visfantin enhanced the expression of ICAM-1 in a dose-dependent manner, and also induced TLR4 up-regulation and IκB-α down-regulation (P＜0.05), with visfantin at dose of 1×10-5mol/L showing the strongest effect. However, pioglitazone inhibited the above effects of visfatin in a dose-dependent manner, with dose of 20 μmol/L having the maximal effect. Conclusion Pioglitazone exerts protective effect on visfantin-induced inflammatory injury in human vascular endothelial cells, which may be due to its blocking TLR4/NF-κB signal pathway.