<jats:p>It is suggested that masticatory dysfunction affects the central nervous system; however, the underlying mechanism remains unknown. Brain‐derived neurotrophic factor (BDNF) and its receptor, TrkB, are known to play important roles in memory and learning. In this study, we examined the effects of mastication on memory, the expression levels of BDNF and TrkB, and the number of neurons in the hippocampus of mice. Male C57 BL/6J mice (3 weeks old) were randomly divided into the control group (N = 7) fed chow pellets and the experimental group (N = 7) fed a liquid diet, which reduces mastication during eating. At 14 weeks of age, we performed a passive avoidance test and found that memory and learning ability were impaired in the experimental group compared with the control group. After the behavioral experiment, brains were harvested and analyzed morphologically and biochemically. In the hippocampus of the experimental group, the expression levels of BDNF were significantly higher, whereas those of TrkB were lower than those of the control group. In the cerebral cortex, these levels remained unchanged between the two groups. The ratio of phospho‐p44/42 ERK/pan ERK, a downstream molecule of BDNF/TrkB signaling, in the experimental group was significantly lower than that of the control group in the cortex and hippocampus. The number of pyramidal neurons in the hippocampus was lower in the experimental group than in the control group. These findings suggest that reduced mastication induced by a liquid diet in early childhood may impair memory and learning ability, accompanied by neuronal loss in the hippocampus. © 2014 Wiley Periodicals, Inc.</jats:p>