Alzheimer's disease is a progressive neurodegenerative disorder characterized by oxidative stress, neuroinflammation and synaptic dysfunction, which result in part from the abnormal accumulation of senile plaques and neurofibrillary tangles outside and within cerebral neurons, respectively. Thymoquinone is the main biological component of the volatile oil of Nigella sativa and has anti-inflammatory and antioxidant effects in some neurological diseases. Study objective: To evaluate the neuroprotective potential of thymoquinone on the oxidative stress status of the brain in aluminum chloride induced Alzheimer's disease in rats. materials and methods: Thirty male Sprague Dawley albino rats were used in this study. They were randomly divided into 3 groups. Group 1 (control group). Group 2 (AD group): orally with aluminum chloride (100 mg/kg) for 8 weeks. Group 3 (Thymoquinone /AD group) orally Thymoquinone (10mg/kg) and aluminum chloride (100mg/kg) for 8 weeks. At the end of the experiment, serum levels of Malondialdehyde and Glutathione Peroxidase Enzyme and brain tissue homogenate of tau protein and acetylcholine were determined. Results: In AD group, tau protein, acetylcholine in brain and serum Malondialdehyde were significantly increased with a significant decrease of serum Glutathione Peroxidase Enzyme Co-administration of Thymoquinone with aluminum chloride in Thymoquinone /AD group, significantly decreased AR , tau protein, acetylcholine in brain and serum Malondialdehyde and serum Glutathione Peroxidase Enzyme. Conclusion: Thymoquinone could mitigate the neurodegenerative markers and oxidative stress indices encountered in AD, presumably via its antioxidant and anti-inflammatory effects.