Objective：To investigate the effects of running exercise on the white matter and the myelinated fibers in the white matter of the APP/PS1 double transgenic mouse. Methods：Six-month-old female APP/PS1 transgenic mice were divided into the control group（n=7） and the running group（n=12）. The running group ran for four months. Seven mice were randomly selected from each group. After running exercise，Morris water maze test was used to detect the spatial learning and memory abilities of the mice in both groups. The white matter volume，the total length and total volume of the myelinated fibers in the white matter，the total volume of the myelin sheaths and the total volume of the axons in the white matter were investigated with the accurate three-dimensional quantitative stere－ological methods. Results：After four-month running exercise，the mean escape latency of positioning navigation test in the run－ning group was significantly shortened when compared with that in contol group（P=0.000），while the target zone frequency and the percentage of time in target quadrant of the running group in spatial probe test were significantly increased when compared with those in control group（P=0.000，P=0.009）. When compared with those in control group，the white matter volume，the total volume of the myelinated fibers and the total volume of the axons in the white matter were significantly increased in the running group（P=0.026，P=0.042，P=0.027）. The total length of myelinated fibers and the total volume of myelinated sheath in the white matter were not sta－tistically different between the two groups（P=0.259，P=0.901）. Conclusion：The effects of running exercise on the white matter and the myelinated fibers in the white matter might be an important structural basis for understanding the mechanism for the fact that running exercise could delay Alzheimer’s disease progress.