Introduction: It is well established that upregulation of endothelin type B (ET _B ) receptors in vascular smooth muscle cells plays a role in pathophysiological artery remodeling as response to ischemia and atherosclerosis. This study aimed to investigate the ET _B receptors function and localization under normal physiological remodeling. Specifically, in the guinea pig uterine arteries during pregnancy. Methods: Uterine artery contractility was assessed with sarafotoxin 6c and endothelin-1 in wire-myography in uterine arteries from non-pregnant and pregnant guinea pigs at gestational day 37 ± 5. Localization of ET _B receptors, proliferation marker Ki-67, and SMC differentiation marker SM22α in uterine arteries were investigated with immunohistochemistry. Results: Uterine arteries from pregnant guinea pigs showed significantly increased ET _B receptor-mediated vasoconstriction compared to uterine arteries from non-pregnant and to coronary arteries from pregnant guinea pigs (p < 0.001), suggesting that ET _B -receptor upregulation in uterine artery SMCs is a normal physiological mechanism taking place during remodeling. Furthermore, uterine arteries from pregnant guinea pigs showed enhanced expression of ET _B receptors, high density of Ki-67 positive SMCs and sparse SM22α staining in SMCs localized in the outer layer of the vessel wall. Discussion: Our results suggest that ET _B receptors are expressed in dedifferentiated proliferating SMCs of uterine arteries in pregnant guinea pigs. This study provides novel insight into the function and expression of ET _B receptors in uterine vascular remodeling during pregnancy.