Alzheimer's disease (AD) is one of the neurodegenerative diseases associated with reduced cognitive function and inflammation. The aim of this study was to investigate the effect of twelve weeks of regular versus complex voluntary wheel runing on the amount of interleukin-10 and hippocampus tissue damage, memory function and depression in Alzheimer's model rats. 60 male Wistar rats (4-6 weeks old) were randomly divided into six groups including Control-Healthy (C-H), Control-Alzheimer (C-ALZ), Simple Wheel-Healthy (SWheel-H), Complex Wheel-Healthy (CWheel-H), Simple Wheel-Alzheimer (SWheel-ALZ) and Complex Wheel -Alzheimer (CWheel-ALZ). After inducing AD via STZicv injection and after the confirmation of disease by shuttle box test, regular and complex voluntary wheel running were experinced for 12 weeks. Depression and spatial memory function were respectively evaluated with tail suspension and Morris Water Maze tests and hippocampal IL-10 level and CA1 histology were also evaluated using ELISA and optic methods. Data were compared using one-way analysis of variance and Tukey's post hoc test. In the AD groups, the spatial memory funtion and hypocampal IL-10 level were higher, meanwhile; the depperession level and hypocampal CA1 tissue damage were lower than C-ALZ group, following both of the regular and complex voluntary wheel runing training protocols (p<0.05). The complex voluntary wheel runing had more benefits compared to training with regular wheel, in most circumstances (p<0.05). It seems the concurrent stimulation of cognitive funtion along with physical exercise might be more advantagous in AD conditions.