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Mg-based alloys have been considered as potential structural materials for biodegradable implants in orthopedic and cardiovascular applications, particularly when combined with other biocompatible alloying elements. However, the performances of Mg-based alloys in in vitro conditions do not accurately reflect their behavior in an in vivo environment. As such, the present study aimed at evaluating the in vivo behavior of a novel Mg-5Zn-2Nd-0.13Y-0.35Zr alloy designated as ZE52 alloy. In vivo assessment was carried out using cylindrical disks implanted into the sub-cutaneous layer of the skin at the back midline of male Wistar rats for up to 11 weeks. Post-implantation responses evaluated included well-being behavior, blood biochemical tests and histology. The corrosion rate of the implants, expressed in terms of hydrogen gas formation, was evaluated by radiographic assessment and CT examination. Results of the well-being behavioral and blood biochemical tests indicated that the in vivo behavior of ZE52 alloy implants was similar to that of inert Ti-6Al-4V alloy implants introduced into a control group. Moreover, histological analysis did not reveal any severe inflammation, as compared to the reference alloy. However, significant sub-cutaneous gas cavities were observed, indicative of the accelerated degradation of the ZE52 alloy implants. The accelerated degradation was also manifested by the formation of alloy debris that was encapsulated within the gas cavities. Post-implantation gas bubble puncturing resulted in the complete degradation of the Mg-based implants, indicating that the inert nature of the gas prevented accelerated degradation of the alloy before it was naturally absorbed by the body.