To design successful polymeric gene delivery vehicles with good biocompatibility and highly efficientgene transfer ability is one of the great scientific challenges in modern gene therapy. Poly(amidoamine)with pendant aminobutyl group (PAA-BA) has been proved to exhibit high transfection efficiency againstbone marrow stromal cells (BMSCs) in vitro. In this work, based on previous research, PAA-BA'sbiocompatibility including in vitro cytotoxicity determined by effect on BMSCs' morphology, viability,membrane damage and apoptosis/necrosis, and in vivo tissue compatibility determined by muscular andhepatic tissue response were further investigated in comparison to branched polyethylenimine (PEI)25 kDa. The results demonstrated that PAA-BA possess much better cytocompatibility than PEI, yieldingslight cell morphological change, high cell viability and mild effect on cell membrane damage as well asinducing less apoptotic/necrotic cells at optimal N/P ratio. PAA-BA also exhibited better tissue compatibility,reflected by no or less inflammatory response in the site of muscle injection at the same (0.03% w/v)or higher concentration (0.1% w/v) and no hepatic tissue morphological change with normal hepatocytes.We concluded that PAA-BA was promising and safe candidate for in vitro BMSCs gene delivery and hadpotential for in future in vivo gene therapy.