It is well established that impaired glucose metabolism is a frequent complication in patients with hepatic cirrhosis. We have shown previously that leucine, one of the branched-chain amino acids (BCAA), promotes glucose uptake under insulin-free conditions in isolated skeletal muscle from normal rats. The aim of the present study was to evaluate the effects of BCAA on glucose metabolism in a rat model of carbon tetrachloride-induced cirrhosis (CCl₄ rats). Oral glucose tolerance tests (OGTT) were performed on BCAA-treated CCl₄ rats. In the CCl₄ rats, treatment with leucine or isoleucine, but not valine, improved glucose tolerance significantly, with the effect of isoleucine being greater than leucine. Glucose uptake experiments using isolated soleus muscle from the CCl₄ rats revealed that both leucine and isoleucine, but not valine, promoted glucose uptake under insulin-free conditions. In order to clarify the mechanism of the blood glucose-lowering effects of BCAA, we collected the soleus muscles from BCAA-treated CCl₄ rats with or without a glucose load. These samples were used to determine the subcellular location of glucose transporter proteins and glycogen synthase (GS) activity. The oral administration of leucine or isoleucine without a glucose load induced GLUT4 and GLUT1 translocation to the plasma membrane. GS activity was augmented only in leucine-treated rats and was completely inhibited by rapamycin, an inhibitor of mTOR. In summary, we found that leucine and isoleucine improved glucose metabolism in CCl₄ rats by promoting glucose uptake in skeletal muscle. This effect occurred as a result of up-regulation of GLUT4 and 1, and also by mTOR-dependent activation of GS in skeletal muscle. From these results, we consider that BCAA-treatment may have beneficial effects on glucose metabolism in cirrhotic patients.