Duchenne muscular dystrophy is an incurable X linked recessive genetic disease caused by mutations in the dystrophin gene. Many researchers aimed at restoring truncated dystrophin via viral vectors. But the low package capacity and short duration of vectors hampered their clinical application. For these reasons, we constructed four lentiviral vectors, which contained truncated and sequence-optimized dystrophin genes driven by muscle specific promoter. The four lentiviral vectors stably expressed mini-dystrophin in C2C12 muscle cells in vitro. To estimate the treatment effect in vivo, we transferred the lentiviral vectors into neonatal C57BL/10ScSn- Dmd^mdx mice through the local injection. The level of modified dystrophin expression increased, while the distribution of that also restored in treated mice. At the same time they showed the restoration of pull force and the decrease in the number of mononuclear cells. The remissions lasted three to six months in vivo. Moreover, no integration sites of vectors distributed into the oncogenes. In summary, this study has preliminarily demonstrated the feasibility and safety of mini-dystrophin gene carried by lentiviral vector for DMD gene therapy, and provided new strategy to restore truncated dystrophin.