Abstract: Objective To investigate the effect of simulated weightlessness on dorsal root ganglia (DRG) and GDNF in rat model. Methods Eighty male Sprague-Dawley rats were randomly divided into HU group (n=40) and normal control (NC) group (n=40). The experiment lasted for 4 weeks, then L5 DRG was excised, toluidine blue staining was used to detect the changes of nissl body morphology, and GDNF was detected using immunohistochemistry method. GDNF protein expression was measured by Westernblot and GDNF mRNA expression was measured by RT-PCR. Results Nissl body staining showed that, compared with NC group, nissl bodies were stained light, smaller and scattering distribution in HU group. Immunohistochemistry revealed that the number of GDNF and IOD value reduced significantly in HU group (P< 0.05). Western-blot showed that GDNF protein expression in HU group were significantly lower than NC group (P< 0.05). mRNA expression of GDNF decreased significantly in HU group (P< 0.05). Conclusion Four weeks of stimulated weightlessness can cause damaged changes in DRG nissl body morphology and reduction of the number, protein expression and mRNA expression of GDNF, which suggests that simulated weightlessness can cause damage changes in rat dorsal root ganglion.