The purpose of this study was to estimate the influence of epinephrine on in vivo insulin sensitivity and responsiveness after voluntary running. Wistar rats that had previously undergone adrenodemedullation or sham-operation were kept in a sedentary state or trained over a 4 week period. An euglycemic insulin clamp study was performed on adrenodemedullated sedentary rats (ADMX), adrenodemedullated voluntary running rats (ADMX-T), sham-operated voluntary running rats (SHAM-T), and control rats (C) at 18h after the last bout of exercise. The insulin infusion rate was 3.0, 6.0, and 303.0mU/(kgmin), respectively. The blood glucose concentration was maintained constant at basal levels. Metabolic clearance rate of glucose (MCR) was calculated as an index of whole-body insulin action. In the presence of physiological hyperinsulinemia (an insulin infusion rate of 6.0mU/(kgmin)), MCR (ml/(kgmin)) was significantly higher in ADMX-T rats (31.2+/-2.0) than in ADMX rats (19.8+/-0.8, P<0.001) and SHAM-T rats (23.8+/-0.8, P<0.05). Also, the MCR values of SHAM-T and ADMX rats were significantly (P<0.001, and P<0.05, respectively) greater than that of C rats (12.7+/-0.4). At maximal hyperinsulinemia (an insulin infusion rate of 303.0mU/(kgmin)), there was no difference of MCR between ADMX-T rats (49.8+/-4.3) and C rats (38.2+/-2.2). The GDR values of SHAM-T rats (43.5+/-3.7) and ADMX rats (43.5+/-2.1) were also not different from that of C rats. These results provide indirect evidence that epinephrine is one of factors that suppresses increased insulin sensitivity after physical training, although it seems to have no significant influence on insulin responsiveness.