We investigated a possible alteration in the ability of leukocytes to produce reactive oxygen species by stobadine, a pyridoindole antioxidant, in streptozotocin-diabetic rats. The production of free radicals from whole blood was assessed by luminol-enhanced chemiluminescence after stimulation by phorbol myristate acetate. The effects of vitamin E treatment were also evaluated and compared with the effects of combined treatment with stobadine. Diabetes was induced by streptozotocin (55 mg/kg i.p.). Some of diabetic rats and their age-matched controls were treated orally with a low dose of stobadine (24.7 mg/kg/day), vitamin E (400-500 IU/kg/day), or stobadine plus vitamin E for 10 weeks. Stobadine and vitamin E separately produced, to a similar degree, a reduction in diabetes-induced hyperglycemia. The phorbol myristate acetate stimulated chemiluminescence signal was markedly depressed in both moderate and severe diabetic rats. Stobadine treatment prevented this depression of the chemiluminescence response. Vitamin E treatment also eliminated the depression of the chemiluminescence signal in diabetic rats, and the combination with stobadine did not produce further improvement in leukocyte function. These results suggest that stobadine treatment alone is able to produce beneficial effects on leukocyte function and to maintain leukocyte free radical release during diabetes. Copyright (C) 2004 S. Karger AG, Basel.