Objective Autophagy is responsible for the degradation of long-lived proteins and damaged organelles intracellular, even extracellular, and autophagy is proved to have relationship with Alzheimers disease (AD) and aging.The senescence accelerated mouse prone 8 (SAMP8) was a non-genetically modified mice widely used as a rodent model of aging and senile dementia.However, little was known about the age-related changes of autophagy in the brain of SAMP8 mice.Methods Transmission electron microscope was used to observe the age-related ultrastructure and AVs of hippocampal neurons in SAMP8 and SAMR1 mice.We used immunohistochemistry staining and Western-blot analysis to explore the ubiquitin-positive inclusion bodies, the expression of LC3 and Beclin 1 protein in different brain regions of SAMP8 and SAMR1 mice in 2, 7 and 12 months old.Results We found that 7 and 12-month-old SAMP8 mice presented cognitive decline and ubiquitinated proteins enhanced.In the hippocampal neurons of 12-month-old SAMP8 mice, lots of dense clumps and autophagic vacuoles were found in the cytoplasm and axons.The LC3-Ⅱ expression showed an increase in hippocampus and cortex of 7 and 12-month-old SAMP8 mice.The expression of Beclin 1 displayed a significant increase in 7 months old and a decline in 12 months old.Conclusion Based on thesedata, we suggest that the autophagic activity maybe incease reactively at the beginning of AD and then showed a decline with aging, and the pathological changes of 12-month-old SAMP8 mice are more similar to the late-onset AD in the perspective of autophagy.