Exposure to high glucose concentrations increases the mRNA levels of oxygen radical scavenging enzymes in cultured endothelial cells, suggesting a compensatory response to increased free radical production. To test the hypothesis that this response also occurs in vivo, Cu.Zn-superoxide dismutase (Cu.Zn-SOD) and catalase mRNA levels, were measured in the kidneys of Sprague-Dawley rats 17 days after intravenous injection of streptozotocin (60 mg/kg body weight) and compared with those of control rats. Diabetic rats were either left untreated or given differing insulin regimens (2. 3-8, 6-10 IU/day) in two different experiments that were designed to achieve varying degrees of metabolic control. Cu,Zn-SOD and catalase mRNA levels were measured by Northern blot hybridization and standardized by 28S ribosomal RNA determination. Renal Cu,Zn-SOD and catalase mRNA levels were significantly greater in untreated diabetic and in low-dose (2 IU/day) insulin-treated rats than in controls. Treatment with a moderate dose (3-8 IU/day) of insulin normalized catalase but not Cu,Zn-SOD mRNA levels. The highest insulin regimen (6-10 IU/day), in addition to achieving complete metabolic control as evidenced by normal growth and plasma glucose levels, normalized both catalase and Cu,Zn-SOD mRNA levels. Thus, in rats with streptozotocin-induced diabetes Cu,Zn-SOD and catalase renal mRNA levels are greater than in normal rats. This difference is prevented by sufficient insulin dosage to normalize plasma glucose and might be due to an increased production of free radicals.