Bio-ceramic porous scaffolds used in bone tissue engineering are incorporated in vivo by a process of cellular in-growth, followed by cell-mediated degradation and replacement of these scaffolds, in which macrophages and osteoclasts play the key role. Calcium polyphosphate (CPP) is an inorganic polymeric bioceramic which has been increasingly studied as a bone graft. The solution-mediated chemical degradation of strontium-substituted calcium polyphosphate (SCPP) scaffolds is well established in vitro, but an in vitro model of cell-mediated SCPP scaffold degradation has not been investigated. Herein, RAW264.7 (a murine monocyte/macrophage cell line) and osteoclasts were cultured on CPP and SCPP scaffolds. The weight loss and release amount of Sr(2+), Ca(2+) and PO(4)(3-) in a degradation medium indicated that macrophages could accelerate the degradation of SCPP. According to the results from MTT assay and scanning electron microscopy, it was found that a low dose of strontium was beneficial to the proliferation of macrophages, while strontium inhibited the activity of osteoclasts. This study will aid in developing SCPP scaffolds for in vivo bone tissue engineering.