Hypertensive disorders of pregnancy (HDP) is a pathological condition with hypertension and vascular endothelial cell dysfunction (inflammation) during the gestational period. Recently, it was reported that reduction level of plasma histidine-rich glycoprotein (HRG) in human pregnant patients was correlated with the HDP seriousness. HRG is an anti-inflammatory factor that controls the progression of systemic inflammatory pathology such as sepsis syndrome. However, HRG functions in HDP pathology and perinatal physiology have not been clarified yet. In this study, we examined the pregnancy phenotype of HRG gene-deficient (HRG KO) mice to clarify the involvement of plasma HRG on placental formation and hypertensive event during the gestational period. Pregnant HRG KO mice had fetal growth disorder and placental hyperplasia. There was no change in the expression levels of inflammatory factors (IL-1beta, TNF-alpha) in the placenta. On the other hand, the expression level of angiogenic factors (VEGF, PlGF) in placenta increased. In addition, pregnant HRG KO mice had hypertension. These results suggest that HRG may have a physiological function in the gestational period. Pregnant HRG KO mice may be a HDP-like pathological model that causes abnormalities in the placental formation mechanism controlled by HRG.