We have examined the temporal relationship between portacaval anastamosis (PCA), weight gain, changes in skeletal muscle mass and molecular markers of protein synthesis, protein breakdown and satellite cell proliferation and differentiation. Male Sprague Dawley rats with end-to-side PCA (n=24) were compared with sham operated pair fed rats (n=24). Whole body weight, fat free mass and forelimb grip strength were determined at weekly intervals. The skeletal muscle expression of the ubiquitin proteasome system, myostatin, its receptor activin 2b receptor, and its signal cyclin dependant kinase inhibitor p21 (CDKI p21), insulin like growth factor 1 (IGF1), and its receptor IGF1R, and markers of satellite cell proliferation and differentiation were quantified. PCA rats did not gain body weight, had lower lean body mass, forelimb grip strength and gastrocnemius muscle weight. The skeletal muscle expression of the mRNA of ubiquitin proteasome components was higher in PCA rats in the first 2 weeks followed by a lower expression in the subsequent 2 weeks (p<0.01). The mRNA and protein of myostatin, activin 2b receptor, CDKIp21 were higher, while IGF1 and its receptor as well as markers of satellite cell function (PCNA, myoD, myf5 and myogenin) were lower at weeks 3 and 4 following PCA (p<0.05). We conclude that PCA resulted in uninhibited proteolysis in the initial 2 weeks. This was followed by an adaptive response in the later two weeks consisting of an increased expression of myostatin that may have contributed to reduced muscle protein synthesis, impaired satellite cell function and lower skeletal muscle mass.