Abstract： Objective To investigate gene expression profile in peripheral leucocytes of patients with severe preeclampsia (SPE) during 16-20 gestational weeks to see if there are different expression between normal pregnancy and SPE, and to provide the evidence for predicting the pathogenesis of preeclampsia in the future. Methods Eight hundred primipara who accepted pregnancy examination at the First Affiliated of Hospital SUN YAT-SEN University from August 2008 to December 2008 were selected into this study. The gestational age of all objects were confirmed as 16-20 weeks by ultrasonography. And they were followed up until delivered. Six patients developed severe preeclampsia (SPE group); and 40 pregnant women without any complications were chosen as the control. Human genome complementary DNA (cDNA) single-fluorescent chip were used to detect the different gene expression in peripheral leucocytes between normal pregnancy and SPE at 16-20 gestation weeks. Results There were different expressions in 983 genes between SPE group and control group, among which 719 genes were up-regulated and 264 genes were down-regulated in the SPE group. Up-regulating genes mainly involved in immunity, coagulation and fibrinolysis, signal transduction, cell adhesion, transcription and protein synthesis; and the expression of platelet and T cell activation antigen 1 (PTA1/CD226), bactericidal/permeability increasing protein (BPI), interleukin-8 (IL-8), protein kinase C (PKC), lymphocyte antigen 75 (LY-75), mucoprotein and EGFR pathway substrate 8 (EPS8) were significantly increased in SPE patients. Down-regulating genes mainly involved in apoptosis, calcium metabolism, lipid metabolism and cell transformation; and the expression of adrenomedullin (ADM), killer cell immunoglobulin-like receptors (KIR), vitamin D receptor (VDR), adipose differentiation-related protein (ADRP), parathyroid hormone (PTH) and mitogen-activated protein kinase kinase 4 (MKK4) were significantly decreased in SPE patients. Conclusions The gene expressions of peripheral leucocytes in pre-eclampsia patients were different from those of normal pregnant women during 16-20 gestational weeks. Gene CD226, BPI, IL-8, PKC, ADM, KIR and VDR might participate in the pathogenesis of SPE which should be further investigated.