Myostatin is expressed predominantly in skeletal muscle and at significantly lower levels in adipose tissue. The loss of myostatin by gene disruption prevents an age-related increase in adipose tissue mass and partially attenuates the obese and diabetic phenotypes. Inhibition of myostatin signaling could be useful to prevent and/or treat obesity and diabetes. Male OLETF and LETO rats as non-diabetic controls were treated with or without ALA (100 mg/kg per day) and/or insulin (2 U/kg body weight per day) for 8 weeks from their age of 24 weeks. Using quantitative real-time polymerization chain reaction, insulin might increase ActRIIb and FSTL3 in skeletal muscle of diabetes rats partially through enhancing IGF1 and IGF-IR gene expression. Although oral intake of ALA might decrease body fat accumulation, larger amount of skeletal muscle mass from gastrocnemius relatively saved compared with insulin-alone treated group and control group. Myostatin, ActRII and FSTL3 gene expression with ALA-treated group might increase in epididymal fat tissue relation to decreasing IL15, which inhibits fat deposition via a direct action on adipose tissue in rodents and inhibit or oppose TNF-α mediated pathway in both skeletal muscle and adipose tissue. This present data suggest that ALA had better effect in adipose tissue as energy expenditure and metabolic actions, myostatin signaling may play a role in the response of adipocytes to diabetes.