OBJECTIVE: The pathogenesis of diabetes is closely related to islet beta-cell dysfunction. Lnc-NTF3-5 participates in the occurrence and development of various diseases. However, Lnc-NTF3-54's effect on islet beta-cell dysfunction in high glucose environment remains unclear. MATERIALS AND METHODS: The islet beta cell MIN6 cells were cultured in vitro and randomly divided into control group, high glucose group, NTF3-5 siRNA group, and NTF3-5 group, which was respectively transfected with Lnc-NTF3-5 siRNA and Lnc-NTF3-5 plasmid under high glucose condition. Lnc-NTF3-5 expression was measured by real time PCR and cell proliferation was assessed by MTT assay. In addition, Caspase 3 activity, SOD activity, and ROS content were also detected along with the secretion of IL-10 and IL-1 by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with control group, LncNTF3-5 expression in MIN6 cells was significantly increased in high glucose environment (p<0.05). In high glucose environment, LncNTF3-5 plasmid transfection up-regulated LncNTF3-5 expression, inhibited cell proliferation, increased Caspase 3 activity, and decreased SOD activity. Meanwhile. Lnc-NTF3-5 plasmid also increased ROS content and IL-1 level, and decreased IL-10 level and insulin secretion. Compared with high glucose group, the differences were statistically significant (p<0.05). However. transfection of Lnc-NTF3-5 siRNA down-regulated Lnc-NTF3-5 expression under high glucose environment and reversed the above changes. Compared with high glucose group, the differences were statistically significant (p<0.05). CONCLUSIONS: Lnc-NTF3-5 expression is increased in high glucose environment. Targeting Lnc-NTF3-5 can inhibit islet cell apoptosis, oxidative stress, and promote islet cell proliferation and insulin secretion.