Aim The effect of crocetin on relaxation function of thoracic aorta isolated from hyperlipidemic rabbits was examined and the potential mechanism was explored. Methods Hyperlipidemic rabbit model was established by feeding high lipid diet (HLD) to rabbit.Blood was collected at week 0,2,4,6,8 respectively and serum was used for measurement of nitric oxide(NO) content.At the end of 8th week,serum total cholesterol(TC) and low density lipoprotein cholesterol(LDLC) contents were assayed and thoracic aorta isolated from the rabbit was mounted in an organ bath to measure the endothelium-dependent and-independent relaxations evoked by acetylcholine(Ach) and sodium nitroprusside(SNP) respectively.NO synthase(NOS) activities and mRNA expression of endothelial NO synthase(eNOS) of aorta was determined. Results Endothelium-dependent relaxation of thoracic aorta evoked by Ach was found significantly impaired in merely HLD-treated rabbits with the maximal relaxation of 54% of the control.This impairment was significantly improved by co-treatment with CCT(15,30 mg/kg),with a maximal relaxation of 68% and 80% of the control respectively.Endothelium-independent relaxation induced by SNP maintained comparable in all groups.Compared with HLD group,serum levels of TC and LDLC were decreased in CCT(30 mg/kg) group by 21.6% and 20.2% respectively rather than in CCT(15 mg/kg) group.CCT(15,30 mg/kg) could increase serum NO content by 36.1% and 72.4% respectively at the end of 8th week.Endthelial NOS activity was significantly increased by CCT(30,15 mg/kg) by 76.1% and 47.8% respectively and mRNA expression of eNOS increased by 54.2% and 29.8% respectively.Inducible NOS(iNOS) activity remained unchangeable in all groups. Conclusion CCT could significantly increase the serum NO content and restore endothelium-dependent relaxation in thoracic aorta isolated from hyperlipidemic rabbit.The mechanism under which might be related to increased mRNA expression of vessel eNOS