This study investigated the role of Panax ginseng (PG) on the phorbol myristate acetate (PMA) + calciumionophore A23187-induced hypoxia-inducible factor-1α (HIF-1α) activation, phosphorylation of theextracellular signal-regulated kinase (ERK), and inflammatory cytokine production from the humanmast cell line, HMC-1. HIF-1α and phosphorylation of ERK were observed by Western blotting. Theinflammatory cytokine production was determined by enzyme-linked immunosorbent assay. PGinhibited the PMA+A23187-induced HIF-1α expression and the subsequent production of vascularendothelial growth factor. In addition, PG suppressed PMA+A23187-induced phosphorylation ofERK. We also show that the increased cytokines interleukin (IL)-1β, IL-6, and tumour necrosis factor-αlevel was significantly inhibited by treatment of PG. In the present study, we report for the first timethat PG is an inhibitor of HIF-1α and cytokines on the mast cell-mediated inflammatory responses.