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Background: Bioglass is a highly adoptable bone substitute material which can be combined with so-called therapeutic ions. However, knowledge is poor regarding the influence of therapeutic ions on immune reactions and associated bone healing. Thus, the aim of this work was to investigate the influence of strontium-and copper-doped bioglass on the induction of M1 and M2 macrophages, as well as vascularization. Materials and Methods: Two types of alkali glass were produced based on ICIE16 bioglass via the melt-quench method with the addition of 5 wt% copper or strontium . Pure ICIE16 and 45S5 bioglass were used as control materials. The ion release and chemical composition of the bioglass were investigated, and an in vivo experiment was subcutaneously performed on Sprague-Dawley rats. Results: Scanning electron microscopy revealed significant differences in the surface morphology of the bioglass materials. Energy dispersive X-ray spectroscopy confirmed the efficiency of the doping process by showing the ion-release kinetics. ICIE16-Cu exhibited a higher ion release than ICIE16-Sr. ICIE16-Cu induced low immune cell migration and triggered not only a low number of M1 and M2 macrophages but also of blood vessels. ICIE16-Sr induced higher numbers of M1 macrophages after 30 days. Both bioglass types induced numbers of M2 macrophages comparable with those found in the control groups. Conclusion: Bioglass doping with copper and strontium did not significantly influence the foreign body response nor vascularization of the implantation bed in vivo. However, all the studied bioglass materials seemed to be biocompatible.Bone substitute materials (BSMs) are a small group including biomaterials mainly based on natural or synthetic calcium phosphates and similar compounds (1). Bioactive glass is a specific subgroup which has been shown to be a good BSM due to its optimal bonding to newly formed bone tissue and due to the formation of a hydroxycarbonate apatite layer which supports bone regeneration (2). Since the invention of bioactive glass materials in the 1970s by Professor Larry L. Hench, with 45S5 ® bioglass being one of the first developed materials, much research has been conducted on bioactive glass (3). Silicate-based bioactive glass and glass ceramics, such as Perioglas ® (4) and Ceravital ® (5, 6), have been clinically used as BSMs for several decades. Nevertheless, 2149