Objective To investigate different behavioral activities among four species of mice in three trials ( open field test，tail suspension test and forced swimming test ) ，and provide a reference in the research on new antidepressant． Methods Different locomotion activity and exploration in a novel environment of C57BL /6，BALB / c，ICR，and KM mice were investigated by open field with an automated video detecting system，and tail suspension test and forced swimming test were performed to determine their state of“behavioral despair”． Results In the open field test，the total duration of movement，speed and movement distance of BALB / c，ICR and KM mice were significantly higher than that of C57BL /6 mice ( P ＜ 0. 05) ，and their number of rearing also was significantly more than that of C57BL /6 mice ( P ＜0. 05) ; the immobility time of C57BL /6 mice was significantly longer than that of the other three species of mice measured by tail suspension test ( P ＜ 0. 05) ，but the fixed time of the four species of mice in the forced swimming test were not significantly different． Conclusions The results of this study demonstrate that among the four mice strains tested，C57BL /6 strain displays less spontaneous activity and less exploration in a novel environment． They are likely to cause behavioral despair under acute stress stimulation． Therefore，the C57BL /6 mice may be probably the strain of choice as an acute stress animal model for studies of depression．