In this study, the effects of a series of strontium (Sr)-substituted HA ceramics (0, 1, 5, and 10 mol % Sr substitution) were tested on their physical and biological properties. The crystal structure, composition, and solubility were investigated by TEM, XRD, and solid titration solubility isotherms, respectively. In addition, rat MSCs were cultured with culture media containing ions released from the strontium-substituted HA ceramics as they dissolved. MTT test, alkaline phosphatase activity, and osteoblast transcription factor gene (cbfa1) expression were conducted at different time points. Our results suggested that HA with Sr substitution may change its physical properties, especially its solubility, and consequently enhance undifferentiated MSCs into osteoblast lineage. The results from this and the previous study suggested that 5–10 mol % Sr substitution into HA may be a suitable choice for its use in bone regenerative field. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 562–568, 2012.