Inflammation in rheumatoid arthritis is characterized by immune cell infiltration and cytokine secretion. In particular, mast cells and their cytokines play an important role in the pathogenesis of rheumatoid arthritis. Korean medicine, BaekJeol-Tang (BT) was designed by traditional Korean medicine theory. We already reported therapeutic effect of BT in rheumatoid arthritis. Here, we report the specific underlying mechanism of BT in activated human mast cells, HMC-1 cells. In addition, we report for the first time that BT significantly inhibited the production and mRNA expression of proinflammatory cytokines including thymic stromal lymphopoietin, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α in activated HMC-1 cells. BT also decreased the activation of mitogen-activated protein kinases, nuclear factor-κB, and caspapase-1. Taken together, these results indicate that BT has potential as a regulator of inflammatory reactions for the treatment of arthritis such as osteoarthritis and rheumatoid arthritis.