Aim To explore whether rosiglitazone, exerts beneficial effects on injuries of endothelial cells induced by homocysteine thiolactone （HTL） and to investigate the potential mechanisms. Methods The cultured human umbilical vein endothelial cells （HUVEC） were respectively preincubated with rosiglitazone, and other interference factors including apocynin, captopril, pyrollidine dithiocarbamate （PDTC） and antagonist of peroxisome proliferator activated receptor-γ（PPARγ） GW9662 for 1 hour, and then sequentially incubated with HTL （1 mmol/L） for 24 hours. The cell viability, the level of reactive oxygen species （ROS）, the activity of nuclear factor-κB（NF-κB）, the concentration of soluble intercellular adhesion molecule-1（sICAM-1）, the expression of PPARγ mRNA were examined. Results HTL decreased obviously the HUVEC viability, enhanced the level of ROS and activation of NF-κB, the concentration of sICAM-1 and down-regulated the expression of PPARγ mRNA. Preincubation of HUVEC with rosiglitazone （0.001, 0.01, 0.1 mmol/L）, apocynin （0.1 mmol/L）, captopril （0.03 mmol/L）, PDTC （0.1 mmol/L） for 1 hour reversed these effects induced by HTL, compared with alone HTL group （P<0.05 or P<0.01） . Further, co-incubation with PPARγ antagonist GW9662 （0.01 mmol/L）, abolished the protective effects of rosiglitazone on HTL-treated cells. Conclusions Rosiglitazone has protective effects against injuries of endothelial cells induced by HTL, which is related to PPARγ-mediared suppression of oxidative stress.