Aim To investigate the combined effect of mangiferin and ephedrine as well as explore its underlying mechanism in mouse model of allergic asthma.Methods The mouse model of asthma was sensitized and challenged with ovalbumin(OVA).The behaviors of mice during the challenging period were observed.Continuous autonomic activities of mice after 1 h of drug treatment were monitored with the autonomic activity recorder for 14 days.The total and differential cells in peripheral blood were counted.Histological study of lung sections on airway inflammation was carried out with haematoxylin and eosin(HE) staining.The levels of ovalbumin-specific immunoglobulin E(OVA-sIgE) and(Cyclic Adenosine monophosphate) cAMP in serum were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expression of cytokines mainly produced by Th1/Th2 lymphocytes such as IFN-γ and IL-4, IL-5 were semi-quantitatively analyzed with reverse transcription polymerase chain reaction(RT-PCR).Results Combination treatment and mangiferin could reduce the aberrantly autonomic activity caused by ephedrine in mice.Compared with the model group, asthmatic symptoms in all treatment groups could be significantly relieved, the pathological changes of lung tissue were improved and airway inflammation was reduced.The effect of combined treatment was better than that of mangiferin treatment alone.Compared with the model group, the total number of white blood cells(WBC) and the eosinophils(EOS) ratio in peripheral blood in all treatment groups decreased, the level of OVA-sIgE declined and the level of cAMP increased in serum.Combination treatment could lower mRNA expressions of IL-4 and IL-5 from Th2 lymphocytes and increase the mRNA expressions of IFN-γ released by Th1 lymphocytes.Conclusions The effect of combined therapy of mangiferin and ephedrine is better than that of mangiferin treated alone, meanwhile it can reduce the side effects caused by ephedrine.The underlying mechanism is mainly associated with attenuating Th1/Th2 cytokine imbalance and increasing the level of cAMP.