Severe uterine and placental disturbances have been described in diabetes pathology. The relative severity of these changes appears to correlate with high glucose levels in the plasma and incubating environment. In order to characterize changes in eicosanoid production we compared uterine and placental arachidonic acid conversion from control and non-insulin-dependent diabetes mellitus (NIDDM) rats on day 21 of pregnancy, into different prostanoids, namely PGE 2, PGF 2α, TXB 2 (indicating the production of TXA 2) and 6-keto-PGF 1 (indicating the generation of PGI 2). PGE 2, PGF 2α and TXB 2 production was higher and 6-keto-PGF 1α was similar in diabetic compared to control uteri. PLA 2 activity was found diminished in the NIDDM uteri in comparison to control. A role for PLA 2 diminution as a protective mechanism to avoid prostaglandin overproduction in uterine tissue from NIDDM rats is discussed. Placental tissues showed an increment in TXB 2 generation and a decrease in 6-keto PGF 1α level in diabetic rats when compared to control animals. Moreover, when control uterine tissue was incubated in the presence of elevated glucose concentrations (22 mM), similar generation of 6-keto PGF 1α and elevated production of PGE 2, PGF 2α and TXB 2 were found when compared to those incubated with glucose 11 mM. Placental TXB 2 production was higher and 6-keto PGF 1α was lower when control tissues were incubated in the presence of high glucose concentrations. However, high glucose was unable to modify uterine or placental prostanoid production in diabetic rats. We conclude that elevated glucose levels induced an abnormal prostanoid profile in control uteri and placenta, similar to those observed in non-insulin-dependent diabetic tissues.