Objective：To study the effect of apigenin on A549/DDP cells，and to explore the effect and mechanism of apigenin reverse drugs resistance on A549/DDP cells. Methods：The cells were cultured with different concentrations apigenin. A549/DDP cells proliferation and drug sensitivity was detected by MTT asssy. The drug extracellular transport was detected by Rhodamine-123 retention experiment, the P-gp and the LRP expression in the tumor cells was detected by Western blot, and the transcription of MDR1 mRNA and LRP mRNA in the tumor cells was detected by RT-PCR. Results: The apigenin can inhibit the A549/DDP cells proliferation. There were significant differences between the apigenin groups(20,40,80 μmol/L) and the DDP group（P＜0.05）. The DDP’s IC50 with the apigenin was (5.76±0.36) μg/mL in A549/DDP cells. The DDP’s IC50 without the apigenin was (14.33±0.41)μg/mL in A549/DDP cells, and the reversal index was 2.48. The apigenin can make high Rhodamine-123 accumulate in A549/DDP cells, down-regulate the P-gp expression in A549/DDP cells, and decrease the transcription of MDR1 mRNA in A549/DDP cells. Conclusion: The apigenin may inhibit the A549/DDP cells proliferation and to reverse drug resistance in A549/DDP cells, and the mechanism was ralated to decrease the MDR1 mRNA transcription and down-regulate the expression of P-gp that mediated drug extracellular transport.