Introduction: Pre-eclampsia has been further recognized as a syndrome during pregnancy. Recent studies have found that long-chain fatty acid oxidation (FAO) disorders may be associated with some of preeclampsia. However, the mechanism remains unclear. In this study, we investigated the role of FAO and its relationship with oxidative stress and inflammatory signaling pathways in the pathogenesis of preeclampsia. Methods: PE-like groups included ApoC3 transgenic mice with abnormal fatty acid metabolism, classical PE-like models with injection of N omega-nitro-L-arginine-methyl ester (L-NA) or lipopolysaccharide (LPS), and antiphospholipid syndrome (APS) mouse model with beta 2GPI injection. The control group included wild-type mice with normal saline injection. Serum FFA was compared and placental and hepatic LCHAD, p47phox and NF-kappa B mRNA and protein were detected using real-time quantitative PCR and western blot. Results: FFA levels were significantly increased and were positively correlated with P47phox and NF-kappa B mRNA and protein expression in liver of all groups (p < 0.05), except LPS group (p < 0.05) as compared to control. LCHAD mRNA and protein expression in the liver and placenta was significantly increased in ApoC3+NS, ApoC3+L-NA, and beta 2GPI group, whereas decreased in L-NA group (p < 0.05) as compared to the control group. P47phox mRNA, NF-kappa B mRNA, and protein expression in the liver of all groups, except in LPS and in the placenta of beta 2GPI and L-NA groups, significantly increased (p < 0.05). Discussion: FAO disorders were involved in the pathogenesis of pre-eclampsia through oxidative stress and inflammatory endothelial cell injury. 0 2015 Published by Elsevier Ltd.