목적: The aims of this study were to investigate the effect of intra- tympanic injection of isosorbide (IT-ISB) on vestibular function and endolymphatic hydrops in guinea pig model. 방법:Forty male guinea pigs were used. Isosorbide, an osmotic diuretic, was administered via intratympanic injection. And intracochlear concentration was checked after intratympanic injection of isosorbide with different concentration (100, 50 and 25%). Intracochlear concentration of isosorbide was analyzed by high-performance liquid chromatography coupled to refractive index detection. In normal animals, change of middle ear mucosa was microscopically observed after IT- ISB with different concentration of ISB. Histologically, improvement of endolymphatic hydrops was observed after IT-ISB at chronic disease model as well as at acute attack model which was induced by desmopressin injection. Finally, vestibular function was checked with animal rotator in the acute attack models before and after IT-ISB, and was compared to that in normal controls. 결과:Isosorbide rapidly passed through the round window membrane into perilymph after IT-ISB. Similar intracochlear concentration was measured between 50% and 100% ISB at 3h and 6h, however, significantly lower concentration was observed after IT of 25% ISB (Kruskal Wallis test, p = 0.004, 0.005) . In 2 out of 5 animals, middle ear mucosa was grossly swollen 1 week after 100% IT-injection, in which thickness of mucosa was higher than both normal control and those after 50% IT-injection. In chronic disease model, hydrops was reduced after IT-ISB. In acute attack model, vestibular imbalance was recovered after IT-ISB. 결론:Isosorbide can rapidly pass through the round window membrane after IT. IT-50% ISB was safe and effective for animal study. The improvement of hydrops and the recovery of vestibular function were observed in animal hydrops model.