Chemically durable microspheres 20-30 mu m in diameter containing a large amount of yttrium are useful for in situ radiotherapy of cancer, as they can be activated by neutron bombardment to form beta-emitters, and can be injected into the vicinity of the cancer cells to impart a large localized dose of beta-radiation. In this study, preparation of hollow Y2O3 microspheres using an enzymatic reaction was attempted, and the structure and chemical durability of the resulting microspheres were investigated. Hollow Y2O3 microspheres 20-30 mu m in diameter were successfully prepared by this enzymatic method. The outer surface of the microspheres was smooth and dense, and the inner parts had a honeycombed structure. In simulated body fluids at pH 6 and 7, the hollow Y2O3 microspheres showed high chemical durability.