Decreased glomerular proteinase activity may contribute to matrix accumulation in diabetes. Male Sprague-Dawley rats were rendered diabetic by injection of streptozotocin (STZ) 65 mg/kg i.v.; age-matched, sham-injected rats served as controls. Glomeruli from diabetic rats 1 month after STZ injection demonstrated significant decreases in collagenase and cathepsin B activities compared to control glomeruli. Treatment with insulin resulted in a slight (but not significant) increase in collagenase activity and normalized cathepsin B activity. We conclude that decreased glomerular collagenase and cathepsin B activities are present in STZ diabetes. These alterations may contribute to mesangial matrix accumulation.