Objective To explore the differentially expressed genes (DEG) involved in the pathogenesis of preeclampsia(PE). Methods The gene expression profiles of placental tissues from 7 severe PE patients and 7 preterm controls from June to December 2012 were assessed using microarray. Gene ontology(GO)enrichment analysis and pathway analysis were performed to explore the genes and pathways involved in the pathogenesis of PE. Four DEG involved in these biological processes were further verified by quantitative real-time PCR. Results A total of 308 transcripts were significantly differentially expressed. Of these DEG,81 genes(LEPTIN,PAPPA2,CRH,PLIN2,INHA,BCL6,FLT1,CCR7,etc)were up-regulated,and 227 genes(CXCL12,CXCL9,etc)were down-regulated. GO enrichment analysis indicated that the top 3 GO molecular functions were immune response(GO: 0006955,17 DEG),positive regulation of apoptosis(GO: 0043065,11 DEG)and inflammatory response(GO: 0006954,11 DEG). Pathway analysis showed that the top 3 pathways were cell adhesion molecules(11 DEG),cytokine-cytokine receptor interaction(11 DEG),chemokine signaling pathway(8 DEG). Many genes(LEP,FLT1,TFRC,SH3PXD2A, CYP11A1,SEPP1,and so on)involved in oxidative stress were found to be significantly changed. Of these genes,LEP were significantly up-regulated with a fold change of 61.5. The fold changes of FLT1, SH3PXD2A,SEPP1,CYP11A1,TFRC were 8.6,2.2,-2.0,2.7 and-2.8. Four DEG involved in oxidative stress were further verified by quantitative real-time PCR. Conclusions A DEG signature was identified in severe preeclampsia placentas compared with normal controls. The DEG mainly involved in the molecular mechanisms of immune response,oxidative stress and inflammatory response,and were closely associated with the pathogenesis of PE.