INTRODUCTION: Neuro-immune interactions have been recognized to be involved in the development of neuropathic pain induced by chemotherapeutic drugs (CINP). However, its role in pain resolution remains largely unknown, particularly concerning mast cells. OBJECTIVES: To investigate the bidirectional modulation of mast cell Mas-related G protein-coupled receptor B2 (MrgprB2)-mediated neuro-immune interactions in CINP. METHODS: CINP model was established in wild-type mice, Mas-related G protein-coupled receptor D knockout (MrgprD RESULTS: We observed that cisplatin-induced allodynia was significantly inhibited in MrgprB2 CONCLUSIONS: Our research elucidated the bidirectional modulation of MrgprB2-dependent neural immune axis in CINP. This study emphasized that MrgprB2 is a critical target for early intervention in CINP, and highlighted the necessity of considering the mechanism differences at different stages in pain management.