〔Abstract〕 Objective To investigate the effect of hypoxia on human leukocyte antigen-G(HLA-G) and endothelial PAS domain protein-1(EPAS1) in placenta of pregnant rats and its mechanism in pathogenesis of preeclampsia. Methods Experimental grouping and modeling: SD pregnant rats were randomly divided into normoxia group and acute hypoxia group.Both groups were subdivided into different groups of 48 h, 72 h and 1 week; the third group is chronic hypoxia group lasting for 2 weeks or 3 weeks.The preeclampsia model was established by intraperitoneal injection of L-NAME solution.Tail artery blood pressure of pregnant rats was measured with a noninvasive sphygmomanometer, serum alanine aminotransferase(ALT),serum album(ALB),blood urea nitrogen(BUN),creatinine(Cr) and urinary protein in pregnant rats was detected by the automatic biochemical analyzer, HLA-G protein and EPAS1 protein expressions were detected with the immunohistochemical method in the placenta of the pregnant rats. Results (1) The mean systolic blood pressure, mean diastolic blood pressure and urinary protein on the 21 st day of pregnancy in each pre-eclampsia group were significantly higher than those in normal pregnant rats under the same conditions(P<0.05),but hypoxia had no effect on blood pressure and urinary protein;(2) There were differences in ALT and BUN among normal pregnant rats and preeclampsia rats under hypoxic environment, and the difference was statistically significant(P<0.05).In hypoxia environment, the ALT and BUN values of normal pregnant rats and pre-eclampsia rats were shown significant differences, namely, the ALT and BUN values of normal pregnancy and preeclampsia group began to rise after 72 hours, hypoxia induced them to the maximum value in 1 week, and then decreased in 3 weeks, but it was still higher than that of normoxia group(P<0.05).(3) The positive rate of HLA-G protein expression in preeclampsia group was lower than that in normal pregnancy group(P<0.05);Hypoxia also affected the positive rate of HLA-G protein expression in pregnant rats.The positive rate of HLA-G protein decreased first and then increased.(4) The positive rate of EPAS1 protein expression in preeclampsia group was significantly higher than that in normal pregnancy group(P<0.05);Hypoxia also affected the positive rate of EPAS1 protein expression in pregnant rats.The positive rate of EPAS1 protein increased first and then decreased. Conclusion The overall expression of HLA-G protein in placenta of pregnant rats decreased first and then increased under hypoxic environment.Acute hypoxia may aggravate maternal immune aggression to placenta, but after the body adapts to hypoxia, the immune relationship between mother and placenta returns to normal.The overall expression of EPAS1 protein increased first and then decreased.The response of EPAS1 to the high selective pressure of hypoxia may lead to the acclimation to high altitude hypoxia.