This study has attempted to document a specific haemovascular action of gliclazide on the reversal of early diabetic microangiopathy. A prospective double-blind controlled study was performed over 2 years, comparing gliclazide versus placebo in insulin-treated and gliclazide versus glibenclamide in non-insulin-treated diabetic subjects, after a 1-year run-in period. Glycaemic control was not significantly different in gliclazide- and non-gliclazide-treated subjects before or after the commencement of active therapy. Following treatment with gliclazide in 17/32 insulin-treated and 8/17 non-insulin-treated subjects with Albustix-negative proteinuria, there was no difference in retinopathy score, total proteinuria or the renal clearance of creatinine, albumin, transferrin and immunoglobulin G. In the insulin-treated group, progression of retinopathy was observed in approximately one-third of subjects, but no parameter of proteinuria progressed over 2 years. Thus, this study did not detect a reversal of the parameters measured and does not support an action of gliclazide on diabetic microangiopathy, independent of its hypoglycaemic action.