The purpose of this study was to assess the impact of prednisone treatment for 8 weeks on the level of transforming growth factor‐beta 1 (TGF‐β1), hydroxyproline (HYP) concentrations, and level of the mature, nonreducible collagen cross‐link hydroxylysylpyridinoline (HP) in diaphragm muscle from 12‐week‐old mdx mice. Diaphragm muscle from untreated mdx mice had a significantly higher level of TGF‐β1, HYP, and HP cross‐link compared with normal C57BL/10J (control) mice. Prednisone treatment significantly reduced the level of TGF‐β1 and HYP in diaphragm from mdx mice to values similar to control mice, but resulted in a higher level of the HP cross‐link compared with untreated mdx mice. These findings indicate that short‐term treatment of mdx mice with prednisone can attenuate the fibrotic response in diaphragm muscle, possibly by mediating the level of TGF‐β. Although prednisone was beneficial in preventing collagen accumulation, it resulted in a higher level of the HP cross‐link, presumably by decreasing collagen turnover © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 428–432, 2001