Background: There are evidences showing the relation between chronic hypoxia and Alzheimer's disease (AD) as a metabolic neurodegenerative disease. This study was designed to evaluate the effects of chronic hypoxia on factors which characterized in AD to introduce a new model of AD-dementia. Methods and materials: Twenty-four male rats were randomly divided in three groups: Control group (Co), Sham group (Sh), Hypoxia induction group (Hx, exposed to hypoxic chamber [oxygen 8% and nitrogen 92%] for 30 days, 4 h/day). Spatial learning and memory were analyzed using the Morris water maze task. At day 30 after hypoxia period, animals were sacrificed and serum was gathered for pro-inflammatory cytokines (interleukin-1 beta and tumor necrosis factor) measurements and brains were used for molecular and histopathological investigations. Results: According to behavioral studies, a significant impairment was seen in Hx group (P < 0.05). TNF-alpha and IL-1 beta showed a significant enhanced in Hx group comparing with Co group and Sh group (P < 0.05). As well, the gene expression of seladin-1, Tuj1 and the number of seladin-1 +, Tuj1 +neurons significantly decreased and also the mean number of dark neurons significantly increased in CA1 and CA3 regions of hippocampus. Conclusions: In this study, a new model of AD was developed which showed the underlying mechanisms of AD and its relations with chronic hypoxia. Hypoxia for 30 days decreased seladin-1, Tuj1 expression, increased the number of dark neurons, and also induced memory impairment. These results indicated that chronic hypoxia mediated the dementia underlying AD and AD-related pathogenesis in rat.