Abstract: ob＜x＞jective This study aims to clarify that the effects of glial cell line-derived neurotrophic factor (GDNF) on mouse BV2 microglia to secrete tumor-related factors. Methods BV 2 cells were treated with 0, 50, 100, 200 and 500 ng/ml GDNF for 12, 24, 36 and 48 h. Real-time PCR was used to detect the mRNA ex＜x＞pression levels of tumor suppressor factors (TNF-α, IFN-β and IL-10) and tumor promoting factors (IL-1β, TGF-β, HGF and MMP9); enzyme-li＜x＞nked immunosorbent assay (ELISA) was used to verify the protein secretion of TNF-α, IFN-β and IL-1β. The neutralizing antibody of GDNF or GFR-α1 w as used to treat BV2 cells, and the secretion of IL-1β protein was detected by ELISA. Results GDNF significantly reduced the TNF-α and IFN-β mRNA ex＜x＞pression, while significantly increased the IL-1β, TGF-β, MMP9 and IL-10 mRNA ex＜x＞pression in BV2 cells ( P < 0.05) . Moreover, the protein secretion of TNF-α, IFN-β and IL-1β were consistent with the mRNA ex＜x＞pression. 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 secreted high levels of tumor promoting factors and low levels of tumor suppressor factors, and blocking GFR-α1 inhibited GDNF -induced IL-1β protein secretion, indicating that GDNF may remold the tumor microenvironment via GFR-α1 mediated signaling pathways in microglia to promote the glioma progression.