Differences in exploratory, rearing and locomotion activity of ICR, BALB/c and C57BL/6 strain were investigated by a 16-hole board task and an open field with an automated infrared detecting system. ICR mice had the highest response rate while C57BL/6 mice had the lowest. It took less time for ICR mice to get used to a new environment and its performance in memory testing was also superior to C57BL/6 mice. The results confirmed the feasibility of using a hole-board test to assess memory. Comparisons between the trend of rearing and hole-poking activity demonstrated that the rearing behavior of mice, to a certain degree, reflected its exploratory and cognitive ability. Our results provided firm support for the notion that selection of a mouse strain is essential when conducting studies on higher cognitive behavior in mice.