OBJECTIVE : The loss of teeth not only causes damage to oral function but also is associated with cognitive impairment. Previous studies have reported that chewing can increase CBF, and CBF plays an important role in cognitive function. Whether the loss of teeth can lead to cognitive impairment by reducing CBF is unclear. This study aimed to investigate the changes in CBF, glutamate concentration, the expression of neuronal apoptosis-relatedBax/Bcl-2 and Caspase-3 mRNA and pyramidal cells in the hippocampus, as well as behavioral changes after tooth loss in rats. METHODS : Twelve weeks after the extraction of all maxillary molars in rats, their spatial learning and memory were tested by the Morris water maze, the CBF was detected by ASL-MRI and glutamate concentration was detected by HPLC; the expression of neuronal apoptosis-related Bax/Bcl-2 and Caspase-3 mRNA and the number of pyramidal cells in the CA1 region were also measured. RESULTS : Rats with tooth loss exhibited spatial cognitive impairment in the Morris water maze, decreased CBF, increased glutamate levels andBax/Bcl-2 and Caspase-3 mRNA expression in the hippocampus; the number of pyramidal cells in the CA1 region were also reduced. CONCLUSIONS : These findings suggest that the loss of teeth causes spatial cognitive impairment in rats and that the underlying mechanism might be associated with a decrease in CBF and an increase in the glutamate level in the hippocampus.