Mucociliary dysfunction in the tubotympanum is deeply reflected in the clinical manifestations of otitis media with effusion (OME), and clinical application of pharmacological agents with ciliostimulatory action might therefore enhance the mucociliary clearance function of the tubotympanum to more effectively eliminate middle ear effusions to the pharynx. A herbal medicine, sairei-to, enhances the in vitro ciliary activity of the middle ear during culture. However, this ciliostimulatory effect is not always applicable to the mucociliary system in situ, which may be deteriorated following oral administration of sairei-to. The present study therefore aimed at investigating the in vivo effect of sairei-to on the mucociliary system in the tubotympanum of the guinea pig. Thirty healthy guinea pigs were used. Ten animals were treated with oral administration of physiologic saline solution for 14 successive days. The remaining animals were treated with oral administration of 120 or 600 mg/kg body weight of sairei-to for 14 successive days. Each animal was used for examination of the ciliary activity and mucociliary clearance time of the tubotympanum, 24 h after the final treatment. No significant changes in either ciliary activity or mucociliary clearance time of the tubotympanum were observed upon administration of 120 mg/kg of sairei-to, which was equivalent to the clinical human dosage. By contrast, oral administration of 600 mg/kg of sairei-to significantly enhanced the ciliary activity, but failed to significantly accelerate mucociliary clearance in the tubotympanum, although the mean value of the clearance time became shorter. Therefore, our results suggest that sairei-to to some extent stimulates the function of the mucociliary system. In conclusion, the herbal medicine, sairei-to, might be useful in the treatment of OME, and preventive administration of this drug may be a new therapy in the treatment of recurrent OME.