To investigate the effect of vision clues on spatial cognitive ability of mice, 20 healthy Mus musculus (Km) mice were divided into two groups, control group and test group. During the experiment, the control group was trained in the Morris water maze with the visual signals while all the visual reference objects of Morris water maze were removed when the test group was trained. The latencies and swimming paths of the two groups were recorded for comparing the effect of vision clues on spatial cognitive ability of the mice. The results showed that there was no significant difference of swimming speed between the two groups, but both the latencies to find the hidden platform and swimming paths of the test group increased notably compared with the control group during the place navigation testing and probe trial testing (P＜0.05). According to these results, we concluded that vision clues played a critical role on the spatial cognition ability of mice. If the visual reference objects of Morris water maze were removed, the spatial cognitive ability of the mice would decrease, the latencies increased significantly and swimming paths became long and disorder.