Objective: To establish the preparation method of inhalable tetrandrine (TET) dry powders for pulmonary delivery and preliminary clarify its mechanism of increasing the chemosensitivity of cisplatin in A549/DDP cells.Methods: TET was dissolved in 30% ethanol (0.7%, W/V) and micronized with a Büchi 290 Mini Spray-Dryer.The following conditions were used during spray-drying: inlet temperature=130℃, aspirator =100%, pump rate=4.0 mL.min-1.Six kinds of marketed lactose for pulmonary delivery were used to observe the flowability and dispersibility of its combination with TET.The optimized formulation of TET dry powder inhaler (DPI) was established through characterization of its particle size distribution, morphology, hygroscopicity, flowability and aerodynamic performances.In addition, the influences of TET on the anticancer activity of cisplatin in human lung adenocarcinoma cell lines A549 and drug resistant cell lines A549/DDP were investigated by MTT method in detail, respectively.Finally, cell apoptosis and cell cycle assay test were performed to approach the preliminary mechanism of increasing chemosensitivity of TET, too.Results: The sizes of micronized TET particles were in the range of 1 to 5 μm which could meet the requirements of the aerodynamic characteristics for lung delivery.The fine particles fraction and emitted dose of optimized formulation of TET DPI were 78.9±0.8% and 98.1±0.1%, respectively.The results of MTT test in A549 and A549/DDP cells showed that the addition of TET could reduce the IC50 value of cisplatin especially very notable in latter case.The apoptotic rate of cells induced by combination treatment was also ascended but did not show significant differences between A549 and A549/DDP.Interestingly, the addition of TET could obviously prolong the S phase percentages in cell cycle of both tested cells while cisplatin displays anticancer efficacy by inhibiting DNA synthesis.Therefore, the mechanism of increasing chemosensitivity of cisplatin in A549/DDP cells might be partly correlated with the increasing of S-phase by TET.Conclusion: The preparation and evaluation method of inhalable tetrandrine dry powder for pulmonary delivery was successfully established.The chemosensitivity of cisplatin in A549/DDP cells could be improved significantly through the addition of TET, and the mechanism is partly related to the variation of S-phase percentage in cell cycle.The effect of TET on the expression of multi drug resistance (MDR) protein is undergoing.