en Pharmacokinetics/Dynamics Pharmacokinetics/Dynamics Experimental research article Experimental research article <div style="text-align: justify;"><strong>Introduction:</strong> Allopurinol, a xanthine oxidase inhibitor, reduces both plasma uric acid (UA) and oxidative stress, and benzbromarone, a uricosuric agent, reduces the level of plasma UA. This study was designed to evaluate cardiac mechanical and endothelial functions of the allopurinol- and benzbromarone-treated diabetic rats, and to investigate the underlying mechanism (antioxidant or UA lowering activity) of allopurinol beneficial effects. <strong>Methods:</strong> Diabetes was induced by injecting streptozotocin to male Spargue-Dawley rats. Diabetic animals were treated with allopurinol and benzbromarone. After six weeks of treatment, left ventricular systolic/diastolic functions of hearts, contraction/relaxation responses to phenylephrine and acetylcholine of aortae, and serum levels of malondialdehyde, 8-isoprostane-2&alpha; and UA were measured. <strong>Results:</strong> Diabetic cardiomyopathy and vasculopathy were characterized by reduced myocardial performance and decreased aortic endothelial response to the vasorelaxation effect of acetylcholine. The serum levels of malondialdehyde and 8-isoprostane-2&alpha; levels were elevated in diabetic animals. Allopurinol attenuated the diabetes-induced diastolic impairment of the hearts, endothelial dysfunction of the aortae and decreased oxidative stress parameters in serum; however, benzbromarone had none of these effects. Both, allopurinol and benzbromarone, diminished the elevated levels of UA in diabetic animals. <strong>Conclusion:</strong> Allopurinol improved diabetic cardiomyopathy and aortic endothelial cell dysfunction in diabetic animals through antioxidant effects.</div> Allopurinol, Benzbromarone, Cardiomyopathy, Endothelial dysfunction, Diabetes. 1 8 http://ppj.phypha.ir/browse.php?a_code=A-10-1124-1&slc_lang=en&sid=1 Mohammad Fathalipour Fathalipour@sums.ac.ir 3200319475328460029517 3200319475328460029517 No Department of Pharmacology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Hossein Mirkhani mirkhanh@sums.ac.ir 3200319475328460029518 3200319475328460029518 Yes Department of Pharmacology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Mohsen Goharinia M.goharinia@fums.ac.ir 3200319475328460029519 3200319475328460029519 No Department of Pharmacology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran