Introduction Ginseng is an herbal medicine used worldwide and possesses a wide range of pharmacological activities.However its side effect is rarely concerned.The experience of Chinese medicine revealed that taking ginseng in longer term and higher dose could cause fireness, i.e.the ginseng-abused syndrome.Here, the occurrence mechanism of ginsengs fireness was explored based on the comparison of energy metabolism of mice affected by red ginseng (RG), ginseng (GS), ginseng leaves (GL) and American ginseng (AG) which exhibit with different drug properties according to the theory of TCM.Materials and methods KM mice were randomly divided into five groups (n>30 per group) and respectively administrated distilled water or drugs.The indicators of mice appearance were measured at different times of administration, including eye condition, rectal temperature, saliva secretion, urine, stool weight, blood coagulation time and swimming time;Energy metabolism indexes were measured via TSE phenoMaster/LabMaster animal monitoring system, including 24h oxygen consumption of mice (VO2), carbon dioxide production (VCO2) and heat production (H) and energy expenditure (EE).Biochemical indexes of serum and liver were measured by ultraviolet spectrophotometer and microplate reader.Results Mice in RG and GS group exhibited obviously more eye secretion, less in the amount of saliva secretion and urine after 31 days drug administration.Compared with the control group, the swimming times of mice in GS, AG and GL groups significantly prolonged;the clotting time of mice in GL was extended outstandingly;VCO2, H and EE of mice in GS group were obviously increased;Pyruvate content of mice in RG groups showed firstly decreased and then increased;SDH activity of mice in AG and GL groups was significantly inhibited;LDH activity of mice showed no significant difference among different groups;Na+-K+-ATP enzyme activity of RG and GS groups showed up-regulation firstly and then down-regulation;The content of hepatic glycogen of mice in GS and GL groups increased significantly.Conclusion Results demonstrated that RG and GS with warm drug nature could enhance bodys energy metabolism to produce their dryness to the body and liver Na+-K+-ATP enzyme activity may be the chief index for indicating the fireness of ginseng.In addition, our results enlightened that ginseng, especially red ginseng is not suitable for long time application with higher dose.