Alzheimer's disease (AD) is a common neurodegenerative disease that leads to memory and cognitive impairment. Exercise is suggested to prevent it. However, the exact mechanism remains unclear. This study investigated the effect of moderate exercise on cognitive function, oxidative stress and neuro-inflammation in the hippocampal tissue of experimentally-induced AD rats and the possible role of Nuclear Factor Erythroid 2- Related Factor 2 (NRF2) in mediating this effect. Forty adult male albino rats were divided into control and AD groups. Each group is further subdivided into sedentary and exercised ones. AD was induced by intraperitoneal injection with aluminium chloride (70 mg/kg b.w.) for 6 weeks. Exercise protocol was done by swimming 60 min, 5 times a week for 4 weeks. The following parameters were evaluated in all groups: hippocampal tissue assessment of NRF2, amyloid beta, malondialdehyde, interleukin 6 and total antioxidant capacity. Assessment of cognitive performance was done using Morris water maze at weeks 3, 4 and 6 after AD induction. Results revealed significantly lower hippocampal NRF2 and TAC levels with significant higher Aβ, MDA, IL-6 and impaired cognitive dysfunction in sedentary AD rats. These were reversed by swimming exercise. NRF2 was negatively correlated with Aβ, IL-6 and MDA in both AD groups with positive correlation with TAC. In conclusion, moderate swimming exercise exerts neuroprotective effects in AD through improvement of cognitive function, restoration of the antioxidant and anti-inflammatory capacity. The upregulation of NRF2 could mediate these effects. Therefore, targeting NRF2 could be promising as a therapeutic agent for neurodegenerative diseases.