A noninvasive single injection technique for the measurement of glomerular filtration rate (GFR) using technetium99m diethylene triamine pentaacetic acid (DTPA) was developed for use in the rat. GFR measurements obtained by the technique correlated well with those obtained by Cr51 EDTA infusion (R = 0.95, n = 7). The coefficient of variation was 8.4%. GFR was measured over 4 weeks in diabetic and control rats. GFR increased with time in both groups, with no difference between the groups; however, when corrected for body weight, diabetes was associated with an increased GFR (diabetic 13.6 +/- 1.7 vs. control 10.4 +/- 0.1 ml/min/kg p less than 0.001). Insulin treated rats had higher GFRs than untreated diabetics (p less than 0.05), but GFR/kg was reduced to that of nondiabetic controls. High protein intake in diabetic rats caused an increase in GFR after 1 week of diabetes, but this was not sustained by the fourth week. Genetic hypertension and angiotensin converting enzyme (ACE) inhibition with ramipril had no effect on GFR in diabetic rats. We conclude that serial measurement of GFR in the diabetic rat is accurate and reproducible. Genetic hypertension, high protein intake, and ACE inhibition have little effect on GFR in experimental diabetes.