Background: Alzheimer's disease (AD) is regarded as one of the most common neurodegenerative diseases. It is a chronic, slowly progressing neurological illness that inhibits memory, cognition, and behavior.This research aimed to evaluate the protective effect of angiotensin II type I receptor (AT1R) blockers versus vitamin B12 (VB12) on the AD rat model. Methods: Thirty adult local strain male albino rats were randomly subdivided into 5 equal groups: Group I (control): vehicle only. Group II (AlCl3 induced AD group): AlCl3 175 mg/kg orally. Group III: telmisartan + AlCl3, Group IV: vitamin B12 + AlCl3, and Group V: vitamin B12 + telmisartan + AlCl3. Modified T maze test was used to evaluate the animal behavior. Rotarod test was employed to assess the animal muscle strength. In addition, serum and hippocampal level of brain derived neurotropic factor (BDNF) were assessed. Also, serum level of MDA and SOD were measured. Additionally, histopathological examination of hippocampus and brain tissue was performed. Results: AlCl3 administration resulted in changes similar to AD as proved by deterioration in behavioral tests, significant reduction in serum and hippocampal BDNF, serum SOD and significant increase in serum MDA level along with corresponding histopathological changes in hippocampus. Furthermore, vitamin B12 and telmisartan ameliorated the previously measured chemical biomarkers and behavioral parameters. Also, the antioxidant power was enhanced with combination prophylaxis therapy of both vitamin B12 and telmisartan . Conclusion: Angiotens in type 1 receptor blockade by telmisartan and vitamin B12 administration each one alone or both in combination could have a potential prophylactic and/or therapeutic effect in AD.