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Piper betel Linn. leaves were evaluated for its antihistaminic activity, commonly known as Pan, Vidyache Pan or Tamboli. P. betel has a long history of use in India being applied in multiple therapeutic activities like antibacterial, treating eczema, lymphangitis, asthma, treating rheumatism. So selected, the plant P. betel is effective in histaminic activity related diseases, but antihistaminic activity of P. betel is still not scientifically investigated. In the present study, the pharmacological evaluation of ethanolic extract and essential oil extract of leaves of P. betel Linn. has been done for their antihistaminic activity on guinea pig. In isolated guinea pig tracheal chain preparation, there was a right side shift of dose response curve (DRC) of histamine. Chlorpheniramine maleate was used as a standard drug. Moreover extracts of P. betel disturbed histamine aerosol induce bronchoconstriction in whole guinea pig, where essential oil was more effective comparatively to ethanolic extract. Thus from the results obtained in the present investigation, it can be concluded that ethanolic extract and essential oil of P. betel Linn possess antihistaminic activity.