A novel poly(butyl succinate) (PBS) and polylactic acid (PLA) blend with the favorable mechanical and degradable properties may be applied in the field of biomedicine. The purpose of this study was to investigate the in vitro and in vivo biocompatibilities of the PBS/PLA blend for future application. For in vitro analysis, the L929 fibroblasts and bone marrow stem cells (BMSCs) had been chosen to assess the cytocompatibility. The extract of PBS/PLA blend did not show any cytotoxicity to the L929 and BMSCs by Cell Counting Kit-8 and lactate dehydrogenase assays. Meanwhile, the results of the cytocompatibility showed no difference between the PBA/PLA blend and pure PLA and PBS. Subsequently, they were implanted into rats subcutaneously for in vivo study. It was found that similar with pure PLA and PBS, PBS/PLA blend caused the mild inflammation and foreign body reaction in rats during the consecutive 9 month implantation. However, the status of fibrosis surrounding PBS/PLA blend was superior to the pure PLA and PBS. In all, it was demonstrated that the novel PBS/PLA blend had excellent biocompatibilities in vitro and in vivo.