Current therapies for Duchenne muscular dystrophy (DMD) face major obstacles in achieving treatment efficacy. In this study, we tested a macrophage-mediated system to deliver a therapeutic molecule, called leukemia inhibitory factor (LIF), to dystrophic muscle in the mdx mouse model of DMD. Immature hematopoietic progenitors were transduced with a lentiviral vector containing a LIF transgene under control of the CD11b promoter. These modified immature hematopoietic progenitors were then transplanted into mdx mice so that donor-derived macrophages express LIF upon activation via the CD11b promoter sequence. We found differential effects on collagen accumulation in the diaphragm and quadriceps muscles. We also stimulated fibroblasts isolated from quadriceps and diaphragm muscles with LIF and found that LIF stimulation reduced collagen type III expression in fibroblasts from mdx quadriceps only. These findings indicate that our strategy for delivery of potentially therapeutic transgenes to dystrophic muscle can influence muscle pathology but may vary between muscles.