Objective：This study aims to investigate the expression and function of long non-coding RNA ENSMUST00000127391（lncRNA 127391）in mice mesangial cell（MMC）cultured with high glucose. Methods：The recombinant plasmid pCDH-lncRNA 127391 was successfully constructed in our group. In this study，the recombinant plasmid pCDH-lncRNA 127391 and control plasmid pCDH were transfected into MMC cells respectively，and the expression of lncRNA 127391 was detected by RT-qPCR. The fibrosis markers of fibronectin（FN） and type Ⅰ collagen（Col-1） and proliferation markers of Cyclin D1 and proliferating cell nuclear antigen（PCNA） were detected by Western blot. CCK8 assay was used to detect the proliferation of MMC. Flow cytometry was used to study the effect of lncRNA 127391 on the apoptosis of MMC. Results：Overexpression of lncRNA 127391 in MMC cells was successfully constructed. CCK8 showed that the overexpression of lncRNA 127391 decreased the proliferation rate of MMC cells. And the expression of Cyclin D1，proliferating cell nuclear antigen PCNA，FN and Col-1 in MMC cells decreased after overexpression of lncRNA 127391. Flow cytometry showed that the overexpression of lncRNA127391 increased the number of apoptotic MMC cells. The differences were statistically significant（P < 0.05）. Conclusion：lncRNA 127391 can inhibit the proliferation and fibrosis of MMC cells cultured with high glucose.