The aim of this study was to design electrospun poly(D, L-lactic-co-glycolic acid) (PLGA) and poly(L-lactide) (PLLA) fibrous scaffolds with interconnected pore structures that facilitate the attachment and proliferation of rat muscle-derived stem cells (rMDSCs) and to examine their biocompatibility in vitro and in vivo. Electrospun PLGA and PLLA fibrous scaffolds with interconnected pore structures were successfully fabricated in this study. In cell viability tests, rMDSCs attached and proliferated on these scaffolds in vitro. Subsequently, for in vivo biocompatibility tests, electrospun PLGA and PLLA fibrous scaffolds were implanted with rMDSCs into rats. The degradation rate of the PLGA scaffolds was faster than that of PLLA scaffolds in vivo. PLGA and PLLA scaffolds implanted with rMDSCs induced the ingrowth of new vessels and tissues from the recipient and suppressed macrophage-mediated inflammation. These results showed that the electrospun PLGA and PLLA fibrous scaffolds have high porosities, in vitro cell viabilities, in vivo biocompatibilities, and low immune response. This study suggests that electrospun PLGA and PLLA fibrous scaffolds may provide an environment that allows their use in various biomedical applications.