Preeclampsia (PE) continues to be a significant cause of maternal and neonatal morbidity and mortality. Angiotensin II type I receptor autoantibody (AT1-AA) has been reported accompanied by PE women in numerous studies. Therefore, detecting the mechanism of AT1-AA production is the key breakthrough in understanding PE. Deficiency in MFG-E8 has been verified can lead to autoimmune diseases due to dysfunction in macrophage phagocytosis and the production of autoantibodies. In the present study, we examined the expression of MFG-E8 in PE patients. Compared with the control, PE patients had a lower expression of placental MFG-E8 and a higher expression of placental AT1R. Then, we tested the effect of MFG-E8 on AT1-AA production and macrophage phagocytosis of trophoblast apoptosis in PE rats induced by low-dose endotoxin(LPS) and trophoblast model. In vivo, experiments results showed that systolic blood pressure, 24h urinary protein, serum TNF-α,sLFt-1 and AT1-AA levels, and placental trophoblast apoptosis caused by LPS were all significantly alleviated by MFG-E8. Moreover, administrated with MFG-E8 has shown decreased trophoblast apoptosis and AT1R exposure in vitro, and enhanced the phagocytosis of dead trophoblasts by macrophages. That supports the idea that MFG-E8 could be a potential therapeutic target for attenuating AT1-AA and protecting patients from AT1-AA and PE.