We investigated the effect of treadmill exercise training on the levels of Alzheimer's disease (AD)-related protein molecules in the DG and CA1 areas of a rat model of AD, i.c.v. infusion of Aβ1–42 peptide, 2 weeks (250 pmol/day). Aβ infusion markedly increased protein levels of amyloid precursor protein (APP), the secretase beta-site APP cleaving enzyme-1 (BACE-1) and Aβ in the CA1 and DG areas. The results also revealed that 4 weeks of treadmill exercise prevented the increase in the levels of APP, BACE-1 and Aβ proteins in both hippocampal areas. Exercise, however, did not affect the levels of these proteins in normal rats. We suggest that exercise might be changing the equilibrium of APP processing pathway towards the nonpathogenic pathway most probably via increasing BDNF levels in the brain of AD model.