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Objective: To investigate the antihistamine-releasing effect of a peptide isolated from wasp venom of Vespa orientalis. Methods: This peptide was separated from crude venom by chromatography methods and mass spectrometry. Then various concentrations (2, 4, 8, 16, 32, 64, 128 and 256 μmol/L) of the peptide were incubated with mast cells and lactate dehydrogenase assay was performed. Results: No significant effect was observed in lactate dehydrogenase absorbance under 128 μmol/L concentration. This implied that the peptide did not cause cell death in mast cells and consequently, histamine release did not happen. Moreover, the results showed the IC50 of mast cells degranulation at 126 μmol/L, which was approximately high implying that this peptide had high selectivity for normal cells and did not cause histamine release from these cells. Conclusions: This would be a great aim in new drug development, in which an agent acts potentially on its target tissue without activating the immune system.