Placenta is a temporary critical organ related to fetal development and pregnancy outcomes. And epidemiologic data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET). This study aims to explore the molecular mechanism for PPAR signaling pathway in placenta subjected to IVF-ET in the first trimester. Four first trimester placenta samples from double chorionic twins to single reduction in IVF-ET only because of oviducts factors. The other four control placenta samples from double chorionic twin were derived from those unplanned spontaneously conceived pregnancy after the legal termination. Affymetrix HG-U133 Plus 2.0 Array was performed to evaluate the global gene expressions. We confirmed microarray results from 10 significant differential genes using RT-qPCR. And 10 deregulated gene products were stained in the first trimester placenta by immunohistochemistry. These differentially expressed genes in IVF-ET placentas were submitted to functional annotation of clustering tools of bioinformatics resources and gene ontology enrichment analysis. Schematic representation of placental PPAR signaling pathway was labelled by Kyoto Encyclopedia of Genes and Genomes (KEGG). Analysis results of early placental PPAR signaling pathway gene expression from 8 women demonstrated 34 genes with a significant change in expression between IVF-ET and control group, 25 up-regulated; 9 down-regulated. KEGG pathway analysis indicated that IVF-ET manipulation extensively over-activated PPAR signaling pathway. Immune tolerance, trophoblast invasion, syncytia formation, lipid and glucose metabolism, inflammatory response and other complex biological functions were disturbed. RT-qPCR results and proteins staining intensity were consisted with microarray. Placental gene expressions and functions in PPAR signaling pathway were affected by IVF-ET treatment in the first trimester, which may offer a potential mechanism for the pathogenesis of various adverse outcomes during the perinatal period.