Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disorders. Although various biological effects of corticotrophin-releasing hormone (CRH) has in pregnancy have been reported, its activities in patients with ICP are lacking. Here we evaluated CRH and its receptor (CRH-R1) expression in placenta and serum in control and ICP patients, to assess their potential activities in the ICP pathogenesis. Methods and materials: Placental tissues were obtained from the control and ICP patients (10 cases for each group) between 37 and 39 gestational weeks. Immunohistochemistry, Western Blotting and realtime PCR analysis were used to detect the CRH and CRH-R1 expression in placenta. Meanwhile, maternal serums were analyzed for detecting CRH in the control and ICP patients (80 cases for each group) in 34e37 gestational weeks. All data were observed and recorded for comparing and analyzing in control and ICP patients. Results: CRH staining was found in syncytiotrophoblast and feto-placental vascular endothelium cells of placenta, whereas CRH-R1 staining was found in syncytiotrophoblast by using immunohistochemical analysis. The CRH expression level in ICP placenta was significantly lower than those results in controls (P < 0.01). For CRH-R1, CRH mRNA and CRH-R1 mRNA expressions, no statistical differences were found between control and ICP groups (all P > 0.05). Serum CRH levels increased in both control and ICP groups, but the growth rate was limited in ICP group, especially in late pregnancy (P < 0.05). Conclusions: The down-regulation of CRH in ICP placentas and the limited growth rate of CRH in the maternal serum of ICP patients might impair the blood flow regulation of the utero-placental-fetal unit, which might result in poor fetoplacental vascular perfusion and adverse pregnancy outcomes. CRH might play a significant role in the pathogenesis of ICP and provide a new approach to further investigate the etiology of ICP.