Abstract: Objective To establish xenotransplant paclitaxel-resistant models with A549 human lung cancer cells for the detection of drug resistance. Methods A549-taxol cells (5×106 / mL) were injected into the lungs of nude mice. After 3 weeks, survival and tumor growth were recorded. MTT assays were performed to identify the drug-resistant index and drug susceptibility. Real-time PCR and western blotting were undertaken to detect Pgp170 and MMP-7 mRNA and protein expression, respectively. Results GST-π, P-gp170, and MMP-7 expression were significantly increased (P< 0. 001), and the invasiveness of GST-π-treated A549-taxol lung cancer cells was significantly higher than that of untreated A549- taxol cells and the A549-control group. The survival rate and tumor formation of A549-taxol cells were 100% and 85%, respectively. Immunohistochemistry showed that the drug resistance protein was significantly expressed in the A549-taxol group, and was higher than that in A549-control nude mice. Conclusions GST-π, P-gp170, and MMP-7 expression was associated with paclitaxel resistance in lung cancer. Lung orthotopic transplantation has been gradually established, and the current animal model of paclitaxel-resistant lung cancer remained stable, indicating its usefulness for future experiments.