Abstract: Objective:To explore the effect and mechanism of exercise on endoplasmic reticulum stress induced the apoptosis of hippocampus cells in the Alzheimer's disease model rats.Methods:45 normal male SD rats were randomly divided into 3 groups with 15 rats in each group, the sham operation (S) group, the AD model (M) group, the exercise model (E) group.The AD model of rats were established by bilateral hippocampus stereotaxic injection of Aβ25-35.The apoptosis rate of hippocampus cells were detected with terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) , and the protein expressions of GRP78, Caspase-12, Bcl-2 and Bax in hippocampus tissues were analyzed using Western blot.Results:The TUNEL-Positive neurons in hippocampus of rats in the group M significantly increased than that in the group S (P<0.01) .Western blot showed that the protein expressions of GRP78, Caspase-12, and Bax in the group M increased more significantly than that in the group S (P<0.01) and the expressions of Bcl-2 was conversed.After 6 weeks swimming exercise, compared with the group M, the TUNEL-Positive neurons and the protein expressions of GRP78, Caspase-12, and Bax in the group E significantly decreased (P<0.01) and the expressions of Bcl-2 was significantly increased (P<0.01) .Conclusion:The six-week swimming exercise reduced the apoptosis neurons in hippocampus.The mechanism may be that the swimming exercise depress the ER and down-regulated the expressions of GRP78, Caspase-12 and Bax and up-regulated the expressions of Bcl-2 and then promoted the survival of neurons.