Cyclooxygenase-2 (COX-2, encoded by the gene prostaglandin-endoperoxide synthase 2, PTGS2) is a key enzyme in the conversion of arachidonic acid to prostaglandins. The prostaglandins produced by COX-2 are involved in inflammation and pain response in different tissues in the body. Enhanced COX-2 expression had been found in regions of brains from patients with Alzheimer's disease (AD). Here, we proceeded to test the hypothesis that polymorphisms of the PTGS2 gene predispose to AD. IVS5-275 T>G and Ex10+837 T>C in addition to three tagging SNPs from HapMap database, which provided a comprehensive coverage of genetic variations in the PTGS2 gene in Chinese were genotyped among 257 AD patients and 244 age-matched healthy Chinese subjects. Genetic associations were analyzed by chi(2)-test and haplotypes analysis. Although the previously reported protective polymorphism (rs20417, -765 G/C) for AD in PTGS2 gene was not polymorphic in the Chinese population, SNPs in both the promoter (-2319 G>T) and 3' region (Ex10+837 T>C) of PTGS2 were associated with the risk of AD (p=0.01 and 0.03, respectively). Carriers of Ex10+837 T allele had a 1.5-fold increase in the risk of AD. This study suggested that PTGS2 gene was a predisposition gene and arachidonic acid metabolism might be involved in the pathogenesis of AD. It provided further evidence to support a role of inflammation in the development and progression of AD.