Abstract Recent studies have revealed that the property of drug is mainly associated with the body's substance and energy metabolism. The present study aimed to evaluate the drug property of Poria , called Fuling (FL) in traditional Chinese medicine (TCM), in terms of its effects on the substance and energy metabolism in rat models of cold-deficiency and heat-deficiency syndromes, compared with Aconiti Lateralis Radix Praeparaia , called Fuzi (FZ) in TCM, with hot property, and Anemarrhenae Rhizoma , called Zhimu (ZM) in TCM, with cold property, as reference drugs, respectively. The appearance score, toe and rectal temperatures of the animals treated were assessed at different time points. Several indices in vivo correlated with substance and energy metabolism (glucokinas, phosphoglycerate kinase, cytochrome c reductase, cytochrome c oxydase, and Na+-K+-ATPase), endocrine system (triiodothyronine, thyroxine, and 17-hydroxycorticosteroid), nervous system (acetylcholin esterase), and cyclic nucleotide system were determined. The changes in appearance score and indices in vivo suggested the successful establishment of cold-deficiency and heat-deficiency syndrome models. FZ reversed the decreased levels of indices (substance and energy metabolism and endocrine system) and alleviated the syndrome of cold-deficiency model, and ZM showed obviously therapeutic effect on heat-deficiency syndrome (appearance score, substance and energy metabolism, and endocrine system). FL could alleviate cold-deficiency syndrome and raise the decreased levels of glucokinas, phosphoglycerate kinase, cytochrome c reductase and triiodothyronine in cold-deficiency model, but had no significant effect on heat-deficiency syndrome. Drug property of FL was inferred as trending to " flat and warm ", which still need further study. It was advisable to adopt both cold-deficiency and heat-deficiency models to study the drugs with " flat " property. [ABSTRACT FROM AUTHOR]