Cyclooxygenase-2 (COX-2) is the inducible isoenzyme of COX that leads to increased production of prostaglandins and thromboxane, the mediators of inflammation. Controversial data regarding COX levels or activities in the placentas of women with preeclampsia have led us to examine whether a single nucleotide polymorphism (SNP) in the COX-2 gene is associated with the onset of preeclampsia. Two polymorphisms in the promoter region of COX-2 gene were examined by the polymerase chain reaction and restriction fragment length polymorphism in 128 controls and 74 preeclamptic patients. Genotype distribution and allelic frequencies for -765G→C polymorphism of COX-2 gene were significantly different between patients and controls (p=0.000 and p=0.042, respectively). The odds ratio (OR) for preeclampsia risk associated to the -765G allelic variant was 4.07 (95% confidence interval [CI]: 0.89-18.56). The AA genotype of the -1195 A→G variant was present at a significantly higher frequency among all preeclamptic subjects (p=0.000 χ(2): 13.4, OR: 3.44, 95% CI: 1.74-6.77). A moderate linkage was observed between the -765G and -1195A variants (D(0): 0.201; r(2): 0.003). These findings suggest that SNPs, -765G→C and -1195 A→G, on the promoter region of COX-2 gene may reduce the risk of preeclampsia, possibly by affecting the rate of gene expression.