Normal pregnancy is the controlled state of inflammation and this systemic inflammatory response is reported to be more intense in preeclampsia. The current study tested the hypothesis that maternal serum stimulates interleukin 6 (IL-6) production from endothelial cells and that nicotine inhibits these effects. Human umbilical vein endothelial cells (HUVECs) were incubated with or without 0.5% serum from healthy pregnant women at term (n = 5) and treated with or without nicotine (10(-9) to 10(-6) mol/L) in the presence of 0.5% serum. Cell survival was determined by colorimetric assay. Interleukin 6 concentration and nuclear transcription factor kappa B (NF-kB) activities were determined by enzyme-linked immunosorbent assay (ELISA)-based method. Interleukin 6 production by endothelial cells was significantly stimulated in the presence of maternal serum. Nicotine significantly preserved cell survival and suppressed IL-6 production from endothelial cells. Nicotine also significantly inhibited NF-kB activation in endothelial cells. Nicotine inhibited inflammatory reaction through NF-kB suppression in vitro model of maternal vascular endothelium, and this effect may be one of the explanations for the reduced risk of preeclampsia in smokers.