Social isolation stress is known to be closely related to the regulation of glutamate, an excitable neurotransmitter, in relation to degradation of hippocampus. This study was conducted to investigate the effects of exercise on glutamate-NMDAr and PSD-95/nNOS in dentate gyrus of hippocampus of socially isolated rats. For study, male Sprague-Dawley(SD) rats(n=32) were divided into four groups: Group-housed/Control(GC: n=8); Group-housed/Exercise(GE: n=8); Isolated/Control(IC: n=8); Isolated/ Exercise(IC: n=8). After environmental adaptation period(2 weeks), rats in IC and IE were housed in isolated condition for 6weeks. And then, rats in GE and IE subjected to treadmill exercise were for 5days a week over 6weeks, and the speed was gradually increased. After 24hours exercise sessions, rats were sacrificed. Significant increases of glutamate-, NMDA- and nNOS-positive cells in dentate gyrus and p-/t-PSD-95 ratio in hippocampus of IC group, but significantly reversed in IE group. These results show that exercise can be an effective method to control PSD-95/nNOS complex related to NO generation through direct prevention of the glutamate-NMDAr induced by social isolation stress.