Abstract: Objective: To investigate the mechanisms of multidrug resistance in human lung adenocarcinoma cell line A₅₄₉/ADM and the reversion of multidrug resistance with rifamycin.Methods: The expressions of P-glycoprotein(P-gp) and multidrug resistance-associated protein(MRP) were detected with flow cytometry.The resistance to chemotherapeutic drugs and the reversion with rifamycin was evaluated with MTT assay.The accumulation of ADM in A₅₄₉/ADM cells was evaluated with flow cytometry.Results: The expression of P-gp and MRP enhanced significantly(74.8% and 61.2%) compared with A₅₄₉ cells;with rifamycin(8 μg/ml)added,the sensitivity of A₅₄₉/ADM cells to ADM raised by 2.51 times and accumulation of ADM in A₅₄₉/ADM cells was significantly increased.The sensitivity to VCR,DDP and VP-16 increased by 7.38,1.29 and 2.86 times respecitively.Conclusions: A₅₄₉/ADM cells are resistant to many commonly used anti-cancer chemotherapeutic drugs and the resistance might be related to P-gp and MRP overexpression.Rifamycin could reverse the MDR of lung adenocarcinoma cell lines A₅₄₉/ADM.