ABSTRACTAimHochuekkito formula includes four kinds of prescriptions in Japan. It is not known whether all the formulas express the same stimulating effect on the mucosal immune systems of the upper and lower respiratory tracts.MethodsBy using influenza virus‐sensitized BALB/c mice, which are immuno‐compromised with cyclophosphamide, effects of administration of decocted extracts of four kinds of hochuekkito formulas were compared on anti‐influenza antibody titers in nasal cavity and bronchoalveolar fluids. The contribution of inulooligosaccharides to immuno‐modualting effects on T lymphocyes in Peyer's patches and pulmonary immune responses in poly(I:C)‐induced pneumonia mice was also analyzed.ResultsHochuekkito formulas with either Atractylodis lanceae rhizoma (ALR‐hochuekkito) or Atractylodis rhizoma (AtR‐hochuekkito) stimulated anti‐influenza virus‐specific antibody titers in the nasal cavity; however, ALR‐hochuekkito stimulated the production of the antibody titer in lung but AtR‐hochuekkito did not. Longer‐size inulooligosaccharides in ALR‐hochuekkito induced more IFN‐γ‐producing T lymphocytes in Peyer's patches whereas the intermediate‐size inulooligosaccharides in AtR‐hochuekkito induced more IL‐10‐producing T lymphocytes. Oral administration of the intermediate‐size inulooligosaccharides reduced pulmonary inflammation in poly(I:C)‐inoculated mice but not the longer‐size inulooligosaccharides.ConclusionsAll the hochuekkito formulas stimulate the mucosal immune system in upper respiratory tracts whereas the formula with Atractylodis lanceae rhizoma up‐regulates the pulmonary immune system, and inulooligosaccharides from Atractylodis lanceae rhizoma and Atractylodis rhizoma play a crucial role in regulating the pulmonary immune system with the hochuekkito formula.