Mast cells (MCs) are well studied for their roles in allergic and inflammatory disorders. MCs are also identified in the central nervous system (CNS), but have not been examined much. In recent years, growing evidence has shown that central MCs can modulate brain function and behavior in an endogenous homeostatic way. On the one hand, MCs exert protective effects on the development of related brain regions, the maintenance of neuronal activity, and various behaviors like motivation behavior, emotionality and cognition. The changes in the number and activity of central MCs under stressful conditions have relations with different limbs of stress response of brain and behavior. On the other hand, the hypo-activity or hyper-activity of MCs in immunity-related diseases or MCs transgenic animals both promote deleterious outcomes in brain function and behavior, which may be involved in the pathological process of some neuroimmune disorders. Anatomical and functional studies in vitro indicate that there exist bidirectional interactions between MCs and neural cells, including neurons and glial cells. Firstly, MCs and nerves are apposed with spatial gaps of 20 nm or less, an intimate interaction resembling synaptic junctions. Secondly, MCs and nerves also share common activating signals and receptors. On the one hand, MCs contain a variety of biologically active substances, which regulate the activity of the surrounding brain tissues when released through degranulation upon mast cell activation. On the other hand, there exist different kinds of receptors on mast cell membrane, through which MCs can be affected by neurological and immune signaling molecules in the brain. However, the current findings about the crosstalk between mast cell and the CNS are mainly based on studies in vitro. Until now, we know little about how bidirectional communication between mast cell and the CNS regulate brain and behavior in vivo, and its relationship with pathological processes in some immune related psychosomatic diseases. Further studies are needed to elucidate the neurobiology of brain mast cell, which might open new perspectives for the development of therapeutic targets in some neuropsychological diseases.