Chemically durable microspheres containing yttrium and/or phosphorus are useful for intra-arterial radiotherapy. In the present study, we attempted to prepare yttrium phosphate (YPO4) microspheres with high chemical durability as well as smooth surface and investigated their chemical durability in simulated body environment. YPO4 microspheres with smooth surface around 25 μm were successfully obtained, when gelatin droplets containing YPO4 precursor was cooled to be solidified in water-in-oil emulsion and then heat-treated at 1100°C. The chemical durability of the heat-treated microspheres in simulated body fluid at pH =6 and 7 was high enough for clinical application of radioembolic therapy of cancer.