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Objective: Critical effective constituents were identified from Bufei Yishen formula (BYF),a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I,which may have potential bioactive equivalence to BYF.Methods: The active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi),2 (Bushen),3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory.An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of“Groups 1 to 4” according to their pharmacological activity.We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD).Results: We identified 12 active constituents in BYF.The numbers of constituents in Groups 1 to 4 were 3,2,5 and 2,respectively.We identified the optimal ratios of effective constituents within each group.In Group 1,total ginsenosides:Astragalus polysaccharide:astragaloside Ⅳ ratio was 9∶5∶2.In Group 2,icariin:schisandrin B ratio was 100∶12.5.In Group 3,nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4∶30∶6.25∶0∶0.In Group 4,paeoniflorin:paeonol ratio was 4∶1.An orthogonal design was then used to establish the optimal ratios of Group 1,Group 2,Group 3 and Group 4 in ECC of BYF I.The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside Ⅳ:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5∶12.5∶5∶100∶12.5∶4∶30∶6.25∶25∶6.25.A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF.Conclusion: Based on the ECC of traditional Chinese medicine formula method,the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.