Abstract: Objective To investigate the effects of H₂ receptors in the locus ceruleus （LC） on carotid sinus reflex （CSR） resetting resulted from the stress. Methods Male Sprague-Dawley rats were randomly divided into two groups: unstressed （n=8） and stressed group （n=9）. The latter was subjected to unavoidable electric foot-shock twice daily for a week, each session of foot-shock lasted 2 hours. The left and right carotid sinus regions were isolated from the systemic circulation in all animals anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. We observed the changes in CSR performance induced by stress and the effects of microinjection with H₂ receptor selective antagonist, cimetidine （CIM）, into the LC on the responses of CSR to stress. Results Microinjection of CIM （1.5 /μg, in 1 μl） significantly shifted posterior half range of ISP-MAP relationship curve downwards （P＜0.05） and obviously decreased the value of the reflex parameters such as threshold pressure, saturation pressure and ISP at maximum gain （P＜0.05） in the stressed rats. Microinjection with the same dose of CIM into the LC in the unstressed rats did not change CSR performance significantly （P＞0.05）. The changes in the stressed CSR performance resulted from the microinjection of CIM into the LC did not recover the levels of unstressed CSR after injection. Conclusion H₂ receptors in the LC is involved in the stress-induced CSR resetting, and at the same time, the effects of stress on CSR also have other mechanism.