Objective  To investigate the expression changes of provirus integration site 1 for moloney murine  leukemia virus（Pim-1） gene in damaged neurons  in vitro and related molecular basis of neurotrophic factors regulating Pim-1 expression and promoting the neurite regeneration of damaged neurons. Methods Neuro-2a（N-2a）cells were induced into neuron-like N-2a（N-2a-N）cells by retinoic acid，the proliferation of N-2a cells was inhibited by deferoxamine mesylate(DFO), and N-2a-N cells were injured by acrylamide. The N-2a-N cells were divided into normal control group, injury group, ciliary neurotrophic factors (CNTF) group and neuritin (Nrn1) group，with four samples in each group. The phenotype of N-2a cells and the expression of Pim-1 protein in N-2a cells were detected by immunofluorescence cytochemistry, and the expression of Pim-1 in each group was detected by Real-time PCR and Western blotting. Western blotting was used to detect the expression changes of relevant molecules involving in regulating activity of Pim-1, cells survival, apoptosis and axonal regeneration.  Results Cell immunofluorescence showed that N-2a-N cells had neuronal phenotype to express β-Ⅲ tubulin and neurofilament-200, and Pim-1 protein was expressed in N-2a-N cells. N-2a cell proliferation was effectively inhibited by 50 μmol/L DFO, and N-2a-N cell damage model was established by 1 mmol/L acrylamide. Pim-1 gene expression showed a tendency of first decreasing, then increasing, and then decreasing after N-2a-N cells were injured. Compared with the injury group, the proportion of the longest neurite in CNTF group and Nrn1 group increased significantly, the expressions of intracellular signal transducers extracellular regulated protein kinase 1/2 (ERK1/2), phosphorylated extracellular regulated protein kinase 1/2 (p-ERK1/2), signal transducers and activators of transcription 3(STAT3), phosphorylated signal transducers and activators of transcription 3 (p-STAT3), and Pim-1 were up-regulated, the expressions of apoptosis-related molecules cleaved Caspase-3 and Bax were down-regulated, the expression of nti-apoptosis-related molecule Bcl-2 was up-regulated, so the growth-associated protein 43 (GAP-43) protein involved neurite regeneration. Conclusion There is a need to repair damaged N-2a-N cells by overexpressing the Pim-1 gene. CNTF and Nrn1 can activate the ERK1/2 and STAT3 signaling pathways of damaged N-2a-N cells, and then up-regulate the expression of Pim-1 and GAP-43，and then promote cell neurite regeneration.