Denervation alters the metabolism of the extracellular matrix (ECM) in skeletal muscle; however, the underlying mechanisms of ECM remodeling are not fully understood. The aim of this study was to elucidate the dynamic features of the ECM regulatory process in the early phase of denervated skeletal muscle in male Wistar rats. We investigated the expression of collagens (total, type I, and type III), transforming growth factor beta 1 (TGF-β1), and matrix metalloproteases (MMPs) together with their endogenous inhibitors (TIMPs), at the mRNA and/or protein level in the soleus muscles of control animals and at days 3, 7, and 14 post-denervation. Expression of mRNA encoding collagens was decreased at days 3 and 7, and had recovered by day 14, in parallel with total collagen protein content. Content of TGF-β1 protein was elevated sequentially, up to a maximum of 158% at day 14 post-denervation (P < 0.05), as was TIMP-2 mRNA expression (272% at day 14), whereas MMP-1, MMP-2, and TIMP-1 mRNA expression was not affected at any stage. The initial reduction of collagen mRNA may be responsible for hypoactivity caused by the disappearance of contractile function. Recovery of collagen mRNA/protein at day 14 may be due mainly to the suppressive effects of TGF-β1 on collagen degradation via TIMP-2 upregulation.Denervation causes degenerative changes in skeletal muscles, such as a rapid decrease in muscle volume followed by a reduction in the cross-sectional area of myofibers (2, 22, 24), alteration of myofiber types (22), and disarrangement of sarcomere structures (22). Denervation-induced changes are also observed in intramuscular connective tissue. Intramuscular connective-tissue collagen is mainly composed of types I and III (17). The connective tissue has an important role for muscle function. Length-force characteristics have been shown to be altered by the rupture of intramuscular connective tissue after fasciotomy (14). Therefore, changes in the components of intramuscular connective tissues may impair normal skeletal muscle function, often accompanied by a disturbance in joint mobility. Several studies have reported quantitative changes in intramuscular connective tissue subsequent to non-physiological conditions, but results were inconsistent across studies. Denervation (2, 23), immobilization (13, 24), or unloading (19) lead to increases in collagen concentration in rat calf muscles. Deposition of type-I and -III collagen in the perimysium and epimysium of the gastrocnemius muscle was observed at day 7 post-denervation (23). Concentration of hydroxyproline, a major component of collagen protein, was also increased at 1 and