In the brain, histamine is produced mainly in the tuberomammillary nucleus (TMN) and involved in learning/memory, sleep/wakefulness, feeding, and neuroendocrine regulation. Previously, we demonstrated that activation of the histaminergic neurotransmission by histamine H3 receptor inverse agonists promotes the recall of forgotten memories. However, it remains unclear whether histamine neurons are activated during memory recall and whether activation of histamine neurons is required for memory recall. In this study, first, we used fiber photometry to measure the activity of histamine neurons. We introduced GCaMP6s into histamine neurons of HDC-Cre mice and acquired the fluorescence via optic fibers. The mice were subjected to auditory-reward conditioning. The activity of histamine neurons increased when the mice recalled the reward memory by the conditioning tone. Next, we used optogenetics to test whether the activation of histamine neurons is involved in memory recall. We introduced NpHR into histamine neurons of HDC-Cre mice and inhibited their activity. Inhibition of histamine neurons reduced tone-induced licking behavior that is based on recall of reward memory associated with auditory stimulus. These results suggest that histamine neurons contribute to promoting the recall of associative memories.