Objectives: Allergy is an immune dysfunction caused by degranulation from mast cells in the early phase of allergic disease. The purpose of this study was to investigate the anti-allergic effect of fermented Angelicae gigantis Radix in human mast cell line, HMC-1. Method: The Angelicae gigantis Radix was fermented by Lactobacillus acidophilus. The cell toxicity of fermented Angelicae gigantis Radix(FAGR) was determined by MTT assay. The release of β-hexosaminidase from HMC-1 stimulated by phorbol-12-myristate 13-acetate (PMA) plus A23187 was determined by β -hexosaminidase assay. Also, the concentrations of cytokines (interleukin-1β, -6, -8 and tumor necrosis factor-alpha) were measured by enzyme-linked immunosorbent assay. The gene expression of COX-2 from HMC-1 stimulated by phorbol-12-myristate 13-acetate (PMA) plus A23187 was determined by reverse transcription polymerase chain reaction. The release of histamine on substance P-stimulated HMC-1 was measured by histamine assay. Result: The FAGR suppressed the release of β-hexosaminidase, a marker of degranulation, from HMC-1 stimulated by PMA plus A23187. The FAGR inhibited the production of interleukin-1β, -6, -8 and tumor necrosis factor-alpha. The FAGR inhibited the expression of COX-2 mRNA. The FAGR suppressed the release of histamine on substance P-stimulated HMC-1. Conclusion: These results provide that FAGR may be beneficial in the treatment of allergic inflammatory disease.