In this study we tested whether the type 2 diabetes mellitus associated prostaglandin E synthase 2 arginine to histidine polymorphism at position 298 (R298H) influences prostaglandin E2 levels in humans. Fasting prostaglandin E2 was determined in the blood of subjects carrying different genotypes of the R298H polymorphism. Subjects were matched by sex, age, and body mass index. No differences in prostaglandin E2 levels were found with respect to genotypes when considering the whole group. Male homozygous histidine carriers showed elevated prostaglandin E2 levels compared to heterozygous carriers and homozygous arginine carriers (188.2+/-42.4 vs. 80.4+/-26.5pg/ml, p=0.021; and vs. 92.9+/-15.3pg/ml, p=0.11). These differences were not evident in female subjects. In contrast, 6-keto-prostaglandin F1alpha levels as independent marker of arachidonic acid metabolism showed ambiguous results. Nevertheless, preliminary evidence of the prostaglandin E synthase 2 R298H polymorphism possibly influencing prostaglandin E2 blood levels in a gender-specific manner was obtained.