In the present study, the effects of histidine and histamine on food intake were evaluated through intraventricular (ICV) administration in Chinese perch (Siniperca chuatsi), and the primary cells of Chinese perch were stimulated with different concentrations of histidine and histamine. This study examined the food intake changes within 24 hours after ICV, and detected the changes of appetite genes and amino acid sensing signaling pathways. The results showed that histidine and histamine significantly decreased food intake at 12 h post-injection, compared with the control group. Meanwhile, the mRNA expression of npy, gcn2 and atf4 were significantly decreased (P<0.05), whereas the mRNA expression of agrp and mtor were no significant change (P>0.05). At the cellular level, compared with the control group, 1.0, 2.0 and 3.0 mmol/L of histidine obviously inhibited the expression of npy mRNA (P<0.05), and this inhibitory effect increased with increasing concentration; At the same time, 1.0 and 3.0 mmol/L of histidine also significantly inhibited the expression of agrp mRNA (P<0.05). In addition, different concentrations of histamine did not cause changes in npy and agrp mRNA expression (P>0.05). Besides, 2.0 mmol/L of histidine was no significant change the phosphorylation level of protein S6, as the downstream signaling of mTOR pathway. Our results suggest that histidine and histamine can inhibit the food intake of Chinese perch. Histidine suppresses food intake through its conversion into neuronal histamine, and the inhibitory effect of histidine and histamine on food intake might be mediated through down-regulating the expression of appetite-promoting genes.