Background/Aim: The aim of this study was to evaluate the effect of preventing hypertension on renal disease in a model of genetic hypertension and diabetes. Methods: Four-week-old spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes were randomized for no treatment, or for treatment with captopril, losartan or triple therapy (hydrochlorothiazide, reserpine and hydralazine) for 16 weeks. Results: Increase in systolic blood pressure was equally prevented by captopril (128 ± 3 mm Hg), losartan (128 ± 2) and triple therapy (129 ± 2, p < 0.0001). Albuminuria was similarly reduced by captopril (499 (404–659)), losartan (622 (470–976)) and triple therapy (479 (362–600) µg/24 h (p < 0.0001)). Renal fibronectin expression increased in diabetic SHR (125 ± 13 densitometric unit) as compared to the controls (51 ± 9, p < 0.0001), and decreased (p < 0.0001 vs. diabetic SHR) with captopril (32 ± 8), losartan (27 ± 4) and triple therapy (35 ± 6). Conclusion: The prevention of hypertension in diabetic SHR by captopril, losartan or triple therapy was equally efficacious in impeding increase of albuminuria and the expression of renal fibronectin. Under these conditions, tight blood pressure control was the main determinant in attenuating nephropathy.