Aim To explore whether homocysteine thiolactone(HTL)-induced vascular endothelial dysfunctions relate to activation of peroxisome proliferator activated receptor-γ(PPARγ).Methods The endothelium-dependent relaxation(EDR) and non-endothelium-dependent relaxation(n-EDR) of aortic rings in rats induced by acetylcholine and sodium nitroprusside(SNP) were examined respectively.The various biochemical parameters in vascular tissues or blood sera were also analyzed.Results Incubating HTL(10 mmol/L) with aortic rings for 30 min significantly inhibited EDR of isolated aortic rings,reduced nitro oxide(NO) content,increased activity of superoxide dismutase(SOD) and content of malondialdehyd(MDA) in vitro(P<0.01).The incubation of rosiglitazone(1 mmol/L) with aortic rings for 30 minutes prior to adding HTL significantly lessened HTL induced-injuries of EDR,preserved NO content,inhibited elevation of SOD activity and MDA content in aortic tissues(P<0.05 or P<0.01).Incubation of Captopril(0.03 mmol/L) and Apocynin(0.03 mmol/L) with aortic rings for 30 minutes prior to adding HTL respectively also protected the vascular endothelium from injury and the change of biochemistry parameters in aortic tissues(P<0.05 or P<0.01) in vitro.Rats were administered HTL(50 mg/(kg·d)) by gavage for 8 weeks that resulted in an inhibition of EDR of aortic rings,increases of MDA content,reduction of both paraoxonase-1(PON1) activity and NO content(P<0.01),but had no effect on activity of total nitric oxide synthase(TNOS),activity of endothelial nitric oxide synthase(eNOS),activity of induced nitric oxide synthase(iNOS) in sera and activity of erythrocytic SOD(P>0.05).The treatment of rosiglitazone(10,20 or 40 mg/(kg·d)) by gavage prior to gavage of HTL dose-dependently improved EDR of aortic rings injured by HTL in vivo,inhibited elevation of MDA content,recovered PON1 activity and NO content in sera induced by HTL(P<0.05 or P<0.01).The treatment of capropril(20 mg/(kg·d)) and apocynin(200 mg/(kg·d)) also significantly reduced injury of EDR and the changes of biochemistry parameters in sera(P<0.05 or P<0.01).The treatment of HTL in both vivo and vitro had no effect on the non-endothelium-dependent relaxation by SNP(P>0.05).Conclusion HTL-induced vascular endothelial dysfunction may relate to oxidative stress and involve in inhibiting the activation of PPARγ or down-regulating the expression of PPARγ.