Water extracts of eighteen herbal materials and genistein were used to investigate their effects on compound 48/80-induced histamine release in rat peritoneal mast cells (RPMCs). The inhibition effects of histamine release by the water extracts of Ulmus pumila Linne (UP), Lonicera japonica Thunberg (LJT), Angelica gigas Nakai (AGN), Cordyceps militaris (CM), Rehmannia glutinosa Liboschitz (RGL), Liriope platyphylla Wang et Tang (LPWT), Zizyphus jujuba var. inermis Rehder (ZJ) were evaluated by a dose-response assay. LPWT, ZJ, and genistein showed dose-dependent decrease in histamine release at the concentrations of 1 to 1,000 mg/mL, and the inhibition percentage reached up to 31.0, 35.9, and 46.2%, respectively. UP, LJT, AGN, CM, and RGL significantly decreased histamine release at 1 to 100 μg/mL. Among the various combinations, mixture of UP and genistein showed an enhanced inhibition on histamine release.