Thus, the aim of the present study was to investigate the effects of HMB supplementation on dexamethasone-induced skeletal muscle atrophy in vivo. In addition, we evaluated the molecular mechanisms involved in Hydroxyflutamide dexamethasone induced muscle atrophy and the inhibitory effects of HMB supplementation on these molecular events, in the hope that these evaluations would provide information regarding the therapeutic implications of HMB supplementation in a background of glucocorticoid-induced muscle atrophy. Body weight changes and food intakes were measured during the 5-day experimental period. The dexamethasone-treated groups presented progressive weight loss throughout the study as compared with the control group. As was expected, dexamethasone treatment also caused a significant reduction in food intake. Supplementation of HMB or leucine did not prevent body weight loss or influence food intake. To investigate muscle loss after treatment, weights of soleus and gastrocnemius muscles were measured immediately after biopsy. Dexamethasone significantly decreased soleus and gastrocnemius weights, and supplementation of HMB or leucine did not prevent this muscle weight loss. To examine basal serum insulin level changes and glucose homeostasis, we checked serum insulin and glucose levels. Serum glucose levels were significantly increased by dexamethasone, but supplementation with leucine or HMB did not influence this dexamethasone- induced serum glucose increase. Serum insulin levels were Fusidic acid markedly increased by dexamethasone, but neither supplement affected this dexamethasone-induced serum insulin increase. These results suggest that HMB supplementation does not influence dexamethasone-induced glucose or insulin increases. Since dexamethasone is known to deplete myosin heavy chain, which plays an important role in muscle contraction, we measured MyHC protein levels in soleus muscle. Dexamethasone markedly reduced MyHC protein levels, and supplementation with HMB or leucine effectively inhibited this reduction. We further investigated whether reductions in MyHC levels were caused by increased protein degradation or decreased protein synthesis. MyHC mRNA levels were not affected by dexamethasone treatment or supplementation, indicating that the synthesis of MyHC was not affected by treatment or supplementation.