〔Abstract〕 Objective To explore the effect of LncRNA MEG3 in temozolomide(TMZ) resistance of glioma cells. Methods TMZ-resistant glioma cells U87(U87/TMZ) were constructed, qRT-PCR was used to detect the LncRNA MEG3 expression level, and MTT was used to detect the cell proliferation ability. The LncRNA MEG3 in U87/TMZ was overexpressed by liposome method(pcDNA-MEG3 group), the empty vector was transfected as the empty vector group(pcDNA group), and the conventionally cultured U87/TMZ was used as the blank group(Control group),then treated with 10 μg/ml TMZ. The plasmid transfection effect was analyzed by qRT-PCR. The expression of LncRNA MEG3-related protein was confirmed by Western blot. The cell cloning experiment detects the effect of LncRNA MEG3 on cell proliferation. The effect of LncRNA MEG3 on cell invasion was tested by Transwell. The effect of LncRNA MEG3 on cell apoptosis was detected by flow cytometry. And mouse transplant tumor animal model was constructed forin vivoexperiments. Results Compared with U87, the expression level of LncRNA MEG3 in U87/TMZ was lower(P<0.01), and the cell viability of U87/TMZ was higher than that of U87(P<0.01). After overexpression of MEG3 combined with TMZ, compared with the Control group and the pcDNA group, the pcDNA-MEG3 group up-regulated the expression of MEG3 mRNA and p53 protein, and down-regulated the expression of MDM2 protein, and the proliferation and invasion ability of the pcDNA-MEG3 group decreased while the apoptosis ability increased(P<0.01). The construction of mouse transplant tumor animal model showed that the tumor volume and mass of the pcDNA-MEG3 group were reduced compared with the pcDNA group(P<0.01). Conclusion Overexpression of LncRNA MEG3 can attenuate the drug resistance of TMZ-resistant glioma cells.