Abstract: Objective To investigate the effects of glial cell line-derived neurotrophic factor (GDNF) on mouse BV2 microglia cells to secrete tumor-related factors. Methods BV2 cells were treated with 0, 50, 100, 200 and 500 μg/L GDNF for 12, 24, 36 and 48 h. Real-time PCR was used to detect the mRNA levels of tumor suppressor factors tumor necrosis factor α(TNF-α), interferon β (IFN-β) and interleukin 10 (IL-10) and tumor promoting factors IL-1β, transforming growth factor β (TGF-β), hepatocyte growth factor (HGF) and matrix metalloproteinase 9 (MMP9). The neutralizing antibody of GDNF or GFR-α1 was used to treat BV2 cells, and the secretion of IL-1β protein was detected by ELISA. Results GDNF significantly reduced the levels of TNF-α and IFN-β mRNA, while significantly increased the levels of IL-1β, TGF-β, MMP9 and IL-10 mRNA in BV2 cells (P<0.05). Moreover, the secretion of TNF-α, IFN-β and IL-1β protein was consistent with their mRNA expression. Both GDNF and GFR-α1 neutralizing antibodies significantly inhibited the secretion of IL-1β protein, and neutralizing GFR-α1 significantly inhibited the secretion of IL-1β protein induced by GDNF (P<0.05). Conclusions GDNF-treated BV2 microglia cells secret low levels of tumor suppressor factors but high levels of tumor promoting factors, and GFR-α1 blockage inhibits GDNF-induced IL-1β protein secretion, which indicates that GDNF may remold the microenvironment that is conducive to the progression of glioma through GFR-α1 mediated signaling pathway.