This study aimed to investigate the anti-allergic activity and the mechanism of action of Crassirhizomae rhizoma (CR). The extract of CR exhibited potent inhibitory activity in mast cells; its IC50 values were 31.2±1.5μg/ml for rat basophile leukemia (RBL)-2H3 mast cells and 51.5±2.1μg/ml for bone marrow-derived mast cells by antigen stimulation. It also suppressed the expression of TNF-α and IL-4 mRNAs in RBL-2H3 cells. In an in-vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis (PCA), in a dose-dependent manner. With regard to the mechanism of action, CR inhibited the activating phosphorylation of Syk kinase, a key signaling protein for the activation of mast cells. Taken together, these results strongly suggested that the anti-allergic activity of CR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk in mast cells.