Proliferation and differentiation of satellite cells are critical in the regeneration of atrophied muscle following immobilization and aging. We hypothesized that impaired satellite cell function is responsible for the atrophy of skeletal muscle seen in cirrhosis also. Myostatin and insulin like growth factor 1 (IGF1) have been identified to be positive and negative regulators respectively, of satellite cell function. Using a rat model of cirrhosis (portacaval anastamosis or PCA) and sham operated controls, we examined the expression of myostatin, its receptor activinR2b and its downstream messenger, cyclin dependant kinase inhibitor p21 (CDKI p21) as well as IGF1 and its receptor in the gastrocnemius muscle. Expression of proliferating cell nuclear antigen (PCNA), a marker of proliferation, and myogenic regulatory factors (myoD, myf5 and myogenin), markers of differentiation of satellite cells were also measured. Real time polymerase chain reaction for mRNA and western blot assay for protein quantification were performed. PCA rats had lower body weight and gastrocnemius weight compared to sham animals (p<0.05). PCNA and myogenic regulatory factors were lower in PCA rats (p<0.05). Myostatin, activinR2b and CDKI p21 were higher in the PCA animals (p<0.05). The expression of insulin like growth factor 1 and its receptor were lower in liver and skeletal muscle of PCA animals (p<0.05). These data suggest that skeletal muscle atrophy seen in the portacaval shunted rats is a consequence of impaired satellite cell proliferation and differentiation mediated, in part, by higher myostatin and lower IGF1 expression.