Interfacial reaction in a multiple emulsion, was carried out with the aim of preparing hollow hydroxyapatite (HAp) microspheres. The multiple emulsion was a W/O/W emulsion, made of dipotassium hydrogen phosphate solution as an inner aqueous phase, cyclohexane as an oil phase, and calcium nitrate solution as an outer aqueous phase. The phase diagrams of Ca(NO₃)₂-K₂HPO₄-H₂O system were drawn by thermodynamic computations and used to simulate the chemical process in a multiple emulsion for determining the experimental conditions. Single phase HAp was synthesized at an initial pH of 12.0. HAp with a Ca/P ratio was measured by inductively coupled plasma spectroscopy to correspond to 1.49. The product was composed of microspheres of 0.5 to 2 μm in diameter. Each microsphere was composed of acicular particles with an aspect ratio of 2.5-10 with a short axis length of about 20 nm.