This investigation is aimed to determine whether the biosynthesis of H,S, an endogenous vasodilator gas, is altered in the streptozotocin-diabetic rat. Plasma H2S concentration as well as the activity, and expression, of H2S synthesizing enzymes (namely cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthetase (CBS)) were measured in various tissues of non-diabetic, streptozotocin-diabetic and insulin-treated diabetic rats. H2S formation in pancreas and liver was increased in diabetic rats. Both CSE and CBS mRNAs were increased in liver of diabetic animals. Similarly, CBS mRNA was increased in pancreas. Insulin treatment restored the changes in H2S metabolism seen. The findings of this study suggest that the metabolism of H2S in pancreas and liver is altered in the streptozotocin-diabetic rat. This is the first study in which a derangement in H2S biosynthesis in diabetes has been demonstrated. H2S may play a part in the aetiology or development of diabetes in this animal model. (c) 2005 Elsevier Inc. All rights reserved.