In uterine tissue obtained from castrated control and non-insulin dependent diabetic (NIDDM) rats, eicosanoid production and its regulation by glucose levels and by the activity of phospholipase A 2 (PLA 2 ) was assessed. Basal outputs of prostaglandins (PGs) PGE 2 , PGE 1 , PGF 2 α , 6-keto-PGF 1 α (indicating the production of prostacyclin), thromboxane B 2 (TXB 2 ) (indicating the generation of TXA 2 ) and leukotriene B 4 (LTB 4 ) were similar in control and NIDDM uterine preparations as assessed by RIA. When uterine conversion of labelled arachidonate into different prostanoids was evaluated, generation of 6-keto-PGF 1 α , PGE 2 and PGF 2 α was similar in control and NIDDM uterine tissue, while TXB 2 production was higher in the diabetic group. Moreover, when control tissue was incubated in the presence of elevated concentrations of glucose (22 mM) and compared to control tissue incubated in concentrations of glucose 11 mM, similar generation of 6-keto-PGF 1 α , PGE 2 and PGF 2 α was observed, and higher concentrations of TXB 2 were found, similar to those observed in diabetic uterine tissue. When NIDDM uterine tissue was incubated in the presence of glucose 22 mM, no difference in any prostanoid evaluated was observed when compared to values obtained in the presence of glucose 11 mM. In this work we have observed in NIDDM uterine tissue a normal TXA 2 production when evaluated by RIA from endogenous arachidonic acid (AA) and a higher TXA 2 generation from exogenous labelled AA. In addition PLA 2 activity was found diminished in the NIDDM uteri in comparison to control uteri. A role of the diminished PLA 2 as a protective mechanism that avoids TXA 2 overproduction in uterine tissue from NIDDM rats is discussed.