Abnormal activity of atherosclerotic endothelial cells paving luminal surface of blood vessels has been described in many diseases. It has been reported that natural polyunsaturated fatty acids such as docosahexaenoic acid exert therapeutic effects in atherosclerotic condition. Human umbilical vein endothelial cells were treated with 1mM palmitic acid for 48hours and exposed to 40M docosahexaenoic acid for the next 24 hours. Real-time polymerase chain reaction analysis was used to measure the expression of PTX3, iNOS, and eNOS. The level of nitric oxide was detected by Griess reagent. The transcription level of genes participating in coagulation and blood pressure was studied by polymerase chain reaction array. Docosahexaenoic acid improved the survival rate by reducing apoptosis rate (P<.05). Compared with that of the group given palmitic acid, attenuation of proinflammatory status was indicated by reduced interleukin-6 (P<.05) and prostaglandin E-2 levels. All genes PTX3, iNOS, and eNOS were down-regulated after being exposed to docosahexaenoic acid. Nitric oxide contents were not changed in cells exposed to docosahexaenoic acid. Polymerase chain reaction array confirmed the reduction of LPA, PDGF, ITGA2, SERPINE1, and FGA after exposure to docosahexaenoic acid for 24hours (P<.05). Docosahexaenoic acid had potential to blunt atherosclerotic changes in the modulation of genes controlling blood coagulation, pressure, and platelet function.