Objective:To investigate the effect of P38 phosphorylation mediated by microtubules polymerizationon and the mechanism of As2O3 induced apoptosis in cisplatin resistant gastric cancer cells. Methods:Cisplatin resistant cells SGC7901/DDP were produced from parental SGC7901 cells by persistent gradient exposure to cisplatin. CCK8 and flow cytometry assays were performed to detect the cytotoxicity of As2O3. The change in the polymerization and drug－fast of tubulin was observed by immunofluorescence microscopy. Results:CCK8 and flowcytometry assay indicated that,when compared with SGC7901,cisplatin resistant SGC7901/DDP cells enhanced anti－apoptosis capacity to As2O3. The expression level of p－P38 was significantly restrained in SGC7901/DDP cells with As2O3 treatment,whereas it was closely related to stability of microtubules in SGC7901/DDP cells. The inhibition of phosphorylation of P38 in SGC7901 cells significantly reduced tubulin polymerization and apoptosis produced by As2O3 treatment. Conclusion:The development of multidrug resistance in cisplatin resistant SGC7901/DDP cells gastric cancer cells to As2O3 was associated with the phosphorylation of P38 mediated tubulin polymerization,and tubulin polymerization plays an important role in the tolerance of As2O3 by gastric cancer cell.