Magnesium alloys are promising implant materials for use in orthopaedic applications. In the present study, screws made of the Mg-alloy ZEK100 (n = 12) were implanted in rabbit tibiae for four and six weeks, respectively. For degradation analysis, in vivo µ-computed tomography (µCT), a determination of the weight changes and SEM/EDX examinations of the screws were performed. Screw retention forces were verified by uniaxial pull-out tests. Additionally, soft-tissue biocompatibility was estimated using routine histological methods (H&E staining) and the immunohistological characterization of B- and T-cells. After six weeks, a 7.5% weight reduction occurred and, in dependence of the implant surrounding, the volume loss (µCT) reached 9.6% (screw head) and 5.0% for the part of the thread in the marrow cavity. Pull-out forces significantly decreased to 44.4% in comparison with the origin value directly after implantation. Soft tissue reactions were characterized by macrophage and lymphocyte infiltration, whereas T-cells as well as B-cells could be observed. In comparison to MgCa0.8-screws, the degradation rate and inflammatory tissue response were increased and the screw holding power was decreased after six weeks. In conclusion, ZEK100-screws seem to be inferior to MgCa0.8-screws, although their initial strength was more appropriate.