Objective To establish a multiple Alzheimer’s disease (AD) animal model by β Amyloid protein 1-42 (AβSUB>1-42/SUB>) combined with D-galactose (D-gal) injection. Methods Fortyfour 2 monthsold SD male rats were divided randomly to 4 group: peritoneal and lateral ventricle injection of physiological saline served as sham group; peritoneal injection of D-gal or lateral ventricle injection of AβSUB>1-42/SUB> individually served as a single factor AD model; peritoneal injection of D-gal combined with lateral ventricle injection of AβSUB>1-42/SUB> established a multiple AD animal model.Morris water maze test the learning and memory capacities. The changes of neuron number and morphology were detected by toluidine blue staining. The activity of the total antioxidant capacity (T-AOC) in serum and brain tissue homogenate were determined by spectrophotometry. The expression of agedassociated protein receptor (AGER) was detected by immunohistochemistry.Results Comparing with the sham group, AβSUB>1-42/SUB> group and D-gal group, the multiple model group exhibited a prolonged latency period which means a higher degree of cognitive and memory impairment; the neurons of hippocampus and cerebral cortex in multiple model group were reduced significantly and plasmalemma shrink, karyopyknosis and trachychromatic neurons increased; the T-AOC of serum and brain tissue in multiple model group declined obviously; the expression of AGER in cerebral cortex,hippocampus,cerebellar nuclei and cerebellar cortex of the multiple model group increased significantly and the staining of the AGER positive cells was trachychromatic and showed dark brown. Conclusion Injection of AβSUB>1-42/SUB> on D-gal induced neuron