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Objective: To uncover the underlying mechanism of Hewei Jiangni granule (HWJNG) on non-erosive reflux disease (NERD) treatment by examining histological changes, gastrointestinal neurochemicals release and visceral hypersensitivity-related receptor expression in NERD model rats. Methods: A NERD rat model was established via a combination of basal sensitization and acid perfusion. HWJNG treatments at different doses were then administered. Pathological changes to tissues, mast cell (MC) activation, serum levels of esophageal visceral hypersensitivity-related neurochemicals, and tran-sient receptor potential (TRP) receptor mRNA and protein levels were investigated. Results: Compared with the control group, the expression of tryptase in MCs, the changes of intercellular space, and the serum levels of substance P (SP), calcitonin gene-related peptides (CGRP) and proteinase-activated receptor 2 (PAR2) increased in the model group (all P<.05). The expression of TRP vanilloid 1 (Trpv1) mRNA decreased in esophagus and dorsal root ganglia (DRG) of the model group (P ＝.030 &P＝.013), and the expression of TRP melastatin channel subfamily member 8 (Trpm8) mRNA decreased in the esophagus of model group (P<.01). The level of esophageal TRPV1 protein increased in the model group (P < .01) and the level of TRPM8 protein decreased in esophagus and DRG of the model group (both P<.05). Compared with the model group, the serum levels of SP, CGRP, and PAR2 in the medium-dose HWJNG group showed significant decreases (all P < .05). The expression of Trpv1 mRNA in esophagus and DRG of the HWJNG groups and the Omeprazole group remarkably decreased (all P<.05), as was the expression of Trpm8 mRNA in esophagus of the HWJNG groups (all P< .05). Conclusion: HWJNG alleviated visceral hypersensitivity in NERD model rats by regulating TRP-mediated signaling. Our results indicate that HWJNG has potential as a therapeutic agent for NERD.