As a growth regulator, PDGF-BB plays a crucial role in regulating neuronal survival and cell differentiation during embryonic development and in the adulthood. The multiple roles and mechanisms of PDGF-BB are still not known, especially involved in plasticity after spinal cord injury. However, before we can carry out further investigations a transgenic animal model with PDGF-BB down-regulation is needed. In the present study, expressional silencing PDGF-BB was achieved by select predesigning hairpins targeting mouse PDGF-BB genes. Six homozygous transgenic offspring were generated and the protein expressions of PDGF-BB were detected in multiple tissues of these mice. The down-regulated rates of PDGF-BB in different transgenic mice were also evaluated. Results showed that different PDGF-BB expressions were detected in multiple tissues and protein levels of PDGF-BB reduced at different rates by relative to that of wild type ones. The expressions of PDGF-BB proteins in transgenic mice decreased at most by 56%. The present study generated TG mice with PDGF-BB down-regulation and established mice model for systemic exploring the possible roles of PDGF-BB in vivo in different pathology conditions.