In this study, we generated a novel rabbit model for DMD via the zygote injection of Cas9 mRNA and a pair of sgRNAs targeting exon 51 of the DMD gene, and demonstrated that the DMD KO rabbits exhibited almost all hallmarks of the disease observed in DMD patients, including muscular dystrophy, cardiomyopathy and high incidence of premature death. This evidence concerns the gene DMD and Duchenne muscular dystrophy.