Objective To explore the role of the long non-coding RNA ( lncRNA) taurine up-regulated gene 1 (TUG1) in the regulation of microRNA (miR)-137 and nerve injury in rats with focal cerebral ischemia. Methods The dual luciferase assay was used to identify the target sites of miR-137 and TUG1. A rat model of focal cerebral ischemia was established using the Longa thread bolt method. Ischemic rats were randomly divided into the following groups (n= 12): model group, small interfering RNA ( si)-negative control ( NC) group ( 10 μL si-NC), si-TUG1 group ( 10 μL si- TUG1), si-TUG1 + anti-miR-NC group (10 μL si-TUG1 and 10 μL anti-miR-NC), si-TUG1 + anti-miR-137 group (10 μL si-TUG1 and 10 μL anti-miR-137). Another group of 12 rats were used in the sham surgery group. Once every 5 days, three injections and detection on the 16th day. The levels of TUG1 and miR-137 in the hippocampus were detected by real- time fluorescence quantitative PCR (RT-qPCR). Cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride staining. The morphology of hippocampal neurons was observed by hematoxylin-eosin and Nissl staining, and the protein levels of JAK1, STAT1, B-cell lymphoma-2 (BCL-2), BCL-2-associated X protein (BAX) and cysteinyl aspartate-specific proteinase-3 (caspase3) were detected by Western blot. Results Starbase analysis showed that there were complementary binding sites between miR-137 and TUG1, which were verified by the double luciferase assay. In the model group, neurons in the hippocampus were disordered, the number of neurons was decreased, neuronal gaps were larger, some neurons underwent nuclear pyknosis or dissolution, nucleoli disappeared, and the number of Nissl bodies decreased. In the si-TUG1 group, the number of neurons increased, the morphology of neurons recovered, and the number of Nissl bodies increased. Compared with that in the si-TUG1 group, damage to the neurons in the si-TUG1 + anti-miR-137 group was more serious, neuronal gaps were larger, and the number of neurons decreased. Compared with those in the sham surgery group, the cerebral infarction volume; TUG1 RNA; and JAK1, STAT1, BAX, and caspase3 protein levels in the hippocampus were higher in the model and si-NC groups (P<0. 05), and the levels of miR-137 and BCL-2 protein were lower (P<0. 05). Compared with that in the model and si-NC groups, the levels of TUG1, JAK1, STAT1, BAX, and caspase3 in the hippocampus and cerebral infarction volume in the model and si-NC groups were lower (P<0. 05), and the miR-137 and BCL-2 levels in the hippocampus were higher (P<0. 05). Compared with that in the si-TUG1 and si-TUG1 + anti-miR-NC groups, TUG1 RNA and JAK1, STAT1, BAX, and caspase3 protein in the hippocampus and cerebral infarction volume were higher in the model and si-NC groups (P<0. 05), and the level of miR-137 and BCL-2 protein in the hippocampus were lower ( P< 0. 05). Conclusions Interfering with TUG1 lncRNA upregulated miR-137 and alleviated neuronal ischemic morphology and apoptosis in rats with focal cerebral ischemia, thus protecting against nerve injury.