The effects of the antifibrotic drug Halofuginone hydrobromide (Halo) on muscle function, regeneration and cardiorespiratory function were studied using mdx mice. It was hypothesized that Halo treatment would resolve pre-established fibrosis and prevent collagen deposits, improving muscle and cardio-respiratory function. Mice 8-9 mos were treated with saline or Halo for 5 (n = 4/group), 10 (n = 5/group) and 12 weeks (n = 4-5/group). Muscle strength and endurance, respiration and muscle susceptibility to damage were assessed. Tissues were collected from all mice. Additional mice were treated for 10 wks (3-4 wks n = 9-10/group; 8-9 mos n = 8-9/group) for echocardiography. Halo reduced fibrosis. As a consequence, there was muscle repair and damage was reduced. There were functional improvements and disease progression was slowed. There was resolution of pre-existing fibrosis and reduction of new collagen synthesis. This treatment could improve quality of life and lengthen the lifespan of DMD patients.