Preeclampsia is a hypertensive disorder of pregnancy. Abnormal placentation associated with poor placental invasion of the uterine vasculature by trophoblast cells, leading to poor placental perfusion, oxidative stress and inflammation, is implicated in its pathogenesis. A dyslipidemia characterised by low plasma levels of high density lipoproteins (HDL) and elevated triglycerides has been described in preeclampsia. Apolipoprotein A-I (apoA-I), a constituent of HDL is an anti-inflammatory agent. This study investigated whether apoA-I protects against hypertension and adverse placental changes in a pro-inflammatory cytokine (TNF-α) induced model of preeclampsia. Further this study investigated whether apoA-I protects against the inhibitory effect of TNF-α in a human in vitro model of trophoblast invasion. Administration of apoA-I to pregnant mice prior to infusion with TNF-α resulted in a significant reduction in the cytokine induced increase in systolic BP. Magnetic resonance imaging (MRI) measurement of T2 relaxation, a parameter which is tissue specific and sensitive to physiological changes within tissues, showed a reversal of TNF-α induced placental changes. Pre-incubation of endothelial cells with apoA-I protected against the TNF-α induced inhibition of HTR-8/SVneo (trophoblast) cell integration into endothelial (UtMVEC) networks. This data suggests that a healthy lipid profile may affect pregnancy outcomes by priming endothelial cells in preparation for trophoblast invasion.