Objective To observe the pathological changes of brain tissues in the WHBE rabbit model of sporadic Alzheimer disease (AD). Methods Thirty 3 - 4?month old male WHBE rabbits were randomly divided into 3 groups: normal control (NC) group, high cholesterol diet (HCD) group, high cholesterol diet + copper drinking water (HCD + Cu^{2 +}) group, 10 in each group. Another 10 senile (36 -48?month old) male WHBE rabbits were taken as senile group. The NC group and the senile group were fed a normal basic diet, the HCD group fed a 2% cholesterol diet, and the HCD + Cu^{2 +} group fed a 2% cholesterol diet plus 0.12 PPM copper drinking water for 12 weeks. The levels of total cholesterol (TC) and β?amyloid protein (Aβ) 1 -42 were measured at 12 weeks. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the cortex and the hippocampus were detected. In addition, the covered area of Aβ, β?site APP cleaving enzyme 1(BACE1) and phosphorylated tau (p?tau) protein in coronal sections of brain tissues were also observed by immunohistochemical staining. The senile plaques and the neurofibrillary tangles were observed by Congo red and Bielschowsky staining, respectively. Results The body weight of WHBE rabbits in the senile group was significantly higher than that of the NC group ( P < 0.01), and the plasma TC and Aβ1 - 42 in each group were significantly higher than that in the NC group ( P < 0.05, P < 0.01). The activity of SOD in brain tissues was significantly lower than that of NC group ( P < 0.05), and the MDA content was significantly higher than that of NC group ( P < 0.05, P < 0.01). Immunohistochemical staining showed that the covered area of Aβ, BACE1 and p?tau in brain tissues of all groups were significantly higher than that of NC group ( P < 0.05, P < 0.01), and the covered area of BACE1 and p?tau protein in the brain tissues of HCD + Cu^{2 +} group was also significantly higher than that of the HCD group ( P < 0.05, P < 0.01). Congo red and Bielschowsky staining showed that the number of senile plaques and neurofibrillary tangles were observed in the brain tissues of the HCD, HCD + Cu^{2 +} and senile groups. Conclusions High cholesterol diet or supplemented with trace copper drinking water can induce obvious AD pathological changes in WHBE rabbit models of sporadic AD with obvious oxidative damage, increased Aβ deposition and senile plaque in the brain, and pathological changes of tau. WHBE rabbit can be used in the study of animal models of neurodegenerative diseases.