Tadalafil  (TAD)  is  an  FDA-approved  selective  long-acting  phosphodiesterase  5  inhibitor (PDE5-I) for the treatment of male erectile dysfunction (ED). It also helps to improve cognitive function  by  lowering  neuroinflammation  and  amyloid  beta  deposition.  A  bi ological, pharmacological, or physical toxicity that impairs the function of the central and/or peripheral nerve systems is referred to as brain impairment. Aluminum poisoning may affect the brain;, causing aberrant amyloid-beta (Aß)  buildup, neuroinflammation, and  neuronal death. This study included sixty mice divided into three groups. (20 each), control group: Mice were given no medication. aluminum chloride group: Mice were received AlCl3daily at dose (8.5 mg/kg) for  4weeks .Tadalafil and ALCL₃ group: mice were  received tadalafil (20 mg/kg/day) and 
ALCL₃ (8.5 mg/kg) for 4 weeks. Administration of ALCL₃ increases the level of brain Lactate, Pyruvate,  acetylcholinesterase  (AchE),  Gamma-aminobutyric  acid  (GABA)  and  Brain Myeloperoxidase (MPO) activities. Whereas, tadalafil administration showing protective role as  it  causing significant decrease in  all  parameters. From  the obtained results,  it  could be concluded that tadalafil has a neuroprotective effect against aluminum chloride induced brain impairment in mice.