We investigated the effect of locally applied pamidronate disodium on the bone resorption using an experimental cholesteatoma and a locally applicable drug delivery system. Three kinds of locally implantable pamidronate disodium were manufactured as thin sheet, thick sheet and wafer forms using biodegradable and biocompatible poly(lactide-co-glycolide), respectively. Several preparation parameter were customized to achieve a desirable controlled release pattern. Each of thin sheet, thick sheet, or wafer was subcutaneously administered to the retroauricular area adjacent to experimental cholesteatoma, six weeks following the induction. The pamidronate treated group consisted of 10 mongolian gerbils for thin sheet group, 10 for thick sheet group, and 10 for wafer group, respectively. Another ten animals were used for the untreated cholesteatoma group. All animals were sacrificed 4 weeks following the treatment. Harvested temporal bones were examined using light microscope and transmission electron microscope. No significant differences in clinical stages of cholesteatomas were found among the thin sheet, thick sheet and wafer group as well as between the treated and untreated group. Scores of osteoclast number per total bone length in millimeter and percentage of surface occupied by osteoclast per total bone surface were significantly lower in the thick sheet and wafer treated group than in the untreated and thin sheet treated group, respectively (p<0.05). These results will provide fundamental data for the future studies on the development of new pharmaceutical agents against localized bone resorption in aural cholesteatoma.