Objective：The current study intended to examine the antinociceptive effect of growth differentiation factor 15(GDF-15) and to elucidate its possible mechanism of action. Methods：Mice formalin-induced pain model with intrathecal administration of GDF - 15(50 ng)and intraperitoneal administration of GDF - 15(10，30，100 μg/kg)was used in this study to examine the antinociceptive effect of GDF-15. The expression of glial cell-line derived neurotrophic factor receptor alpha-like(GFRAL)which is considered to be the specific receptor of GDF -15 was assessed using Western blot and immunofluorescence techniques. The expression of interleukin (IL)-6，IL-1β，tumor necrosis factor(TNF)-α，prodynorphin(PDYN)and proenkephalin(PENK)in the formalin micespinal cords was also evaluated. Results：Intrathecal administration of GDF -15(50 ng)showed a significant antinociceptive effect informalin-induced tonic pain(p<0.05)but not in formalin-induced acute pain. Intraperitoneal administration of GDF-15(10，30，100 μg/kg)produced a dose - dependent antinociceptive effect in mice formalin -induced tonic pain. GFRAL was expressed in brain，cerebellum and spinal cord，and only in neurons of the spinal cord dorsal horn. Moreover，intrathecal injection of GDF -15 inhibited the expression of pro - inflammatory mediators IL -6(p<0.05)and TNF -α(p<0.05)in the spinal cord of formalin mice. Conclusion：GDF -15 exhibits asignificant antinociceptive effect in formalin -induced inflammatory hyperalgesia and its possible mechanism may be by reducing the expression of pro-inflammatory factors IL-6 and TNF-α.