With current pharmacotherapy, otitis media with effusion (OME) is often recurrent and even develops to become chronic. There is now considerable experimental and clinical evidence that the cilia in the tubotympanum play an important part in the prevention of OME. A herbal medicine, sairei-to, has been shown to stimulate the ciliary activity in vitro, and oral administration of the medicine also stimulated the ciliary activity in the tubotympanum rather than physiological states. This study was designed to investigate whether oral administration of sairei-to could prevent experimental OME in the guinea pig. A total of 120 guinea pigs were used. The control group was treated with intratympanic injection of 0.1 ml of physiologic saline solution. The saline-control group was treated with oral administration of physiologic saline solution for 14 successive days. The low-dosage group and the high-dosage group were treated with oral administration of 120 and 600 mg/kg of sairei-to for 14 successive days, respectively. The saline-control group, the low-dosage group and the high-dosage group were then treated with intratympanic injection of 0.1 ml of lipopolysaccharide solution (100 micrograms/ml) derived from Klebsiella pneumoniae. All 10 animals from the 4 groups were sacrificed 1, 3, and 7 days after the intratympanic injection, to examine ciliary activity, mucociliary clearance time, and mucosal pathology of the tubotympanum. The saline-control group exhibited middle ear effusions and pathologies similar to human OME. The incidence of middle ear effusions in the low-dosage and the high-dosage groups was somewhat reduced compared with the saline-control group. The ciliary activity in the tubotympanum was significantly reduced in the saline-control and low-dosage groups compared with the normal-control group. By contrast, the magnitude of reduction in ciliary activity was much smaller in the high-dosage group. The ciliary activity especially in the Eustachian tube and the middle ear close to the tympanic orifice at 3 and 7 days in the high-dosage group was not significantly different from that in the normal-control group. Mucociliary clearance time in the high-dosage group was not different from that in the normal-control group throughout the observation period. The groups treated with sairei-to, especially the high-dosage group, exhibited much milder pathological changes in the tubotympanum than did the saline-control group. In conclusion, clinical application of sairei-to could be an effective measure to prevent the occurrence of OME and also the recurrence of the disease, especially OME-prone individuals.