Objective: To investigate whether endothelin receptor antagonist Bosentan could reduce the nitroglycerin(NTG) tolerance in rats . Methods: Twenty-eight wistar rats were divided into control group(n=10),Nitroglycerin(NTG) group(n=6), Bosentan group (n=6)and NTG+Bosentan group(n=6).The hypotensive response to sodium nitroprusside(SNP) in different group rats,and the relaxation effect of different concentrations of SNP on isolated aortic rings from different group rats were observed .The endothelin-1 (ET-1) contents of plasma and vascular tissue were measured by the radioimmuno assay method. Results: The hypotention response to SNP was significantly attenuated in NTG group,compared with control group. The hypotensive response to SNP was improved in NTG+Bosentan group, compared with NTG group .The relaxation effect of SNP on isolated rat aortic ring was obviously restored in NTG+Bosentan group,compared with NTG group. The ET-1 contents of plasma and vascular tissue were markedly increased in both NTG+Bosentan group and NTG group compared with control group. Conclusion: Endothelin receptor antagonist Bosentan can prevent against the NTG tolerance .