Aim The nucleus tractus solitarii (NTS) is a central brainstem structure that plays an important role in regulating cardiovascular homeostasis. In this study, we examined whether H1 receptors in the NTS can control the baroreceptor reflex function by modulating synaptic transmission. Methods Cardiac baroreceptor reflex function was assessed before and after the microinjection of 2‐pyridylethylamine (10–25 nmol), a histamine H1 receptor‐specific agonist, into the NTS of urethane‐anaesthetized Wistar rats. The cardiovascular responses induced by l‐glutamate microinjection into the NTS were also examined before and after the NTS administration of 2‐pyridylethylamine. Results Nucleus tractus solitarii microinjections of 2‐pyridylethylamine significantly inhibited the gain of the cardiac baroreceptor reflex and bradycardiac/depressor responses induced by l‐glutamate microinjection into the NTS. These findings suggest that histamine H1 receptors regulate the cardiac baroreceptor reflex in a post‐synaptic manner to inhibit barosensitive NTS neurons. Conclusion Taken together with our previous findings, the present results provide further evidence that histamine may play a role within the NTS in regulating cardiovascular homeostasis.