The up-regulation of angiotensin II AT1 receptors has been implicated as a major mediator in the development of hypertension and progressive nephropathy in experimental diabetes. In spite of the documented potential of garlic treatments in ameliorating diabetic complications, the possible involvement of the angiotensin II AT1 receptor, as a central target for the anti-diabetic potential of garlic, has not been explored. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to the AT1 receptor, as verified by western blotting, indicated in immunohistochemical assays that AT1 receptor labeling was significantly increased in adrenal and renal tissues of control diabetic rats compared to the normal group. The increased AT1 receptor labeling involved all cortical zones and medullary chromaffin cells of the adrenal gland. Except for glomerulii, increased AT1 receptor labeling was also evident in proximal convoluted tubules in the renal cortex, and all tubular segments and interstitial cells outlining the vasa recta bundles in the inner stripe of the outer renal medulla. Compared with control diabetic rats, the labeling of the AT1 receptor in the garlic-treated diabetic group was significantly reduced throughout adrenal and renal regions to levels comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced AT1 receptor up-regulation may be implicated in reversing the detrimental consequences of excessive Ang II signaling, manifested by the development of hypertension and nephropathy.