Abstract: Objective To investigate the effects of venlafaxine on chemotherapy-induced neuropathic pain and provide experimental evidence for clinical treatment. Methods Oxaliplatin was administered at 4 mg/kg,twice-weekly for four weeks by lateral tail vein to induce nociceptive peripheral neuropathy in 30 Sprague-Dawley rats, and then rats were randomly divided into three groups：saline group, venlafaxine 7.5 mg/kg group and venlafaxine 15 mg/kg group.Venlafaxine was administered orally once a day for 4 weeks.The paw reflex threshold,as pain response indicators after mechanical stimulation (mechanical withdrawal threshold,MWT) was detected by the von Frey cilia method.The μ,κ and δ opioid receptor expression in L5 dorsal root ganglion were analyzed by immunohistochemistry method. Results Venlafaxine significantly increased the MWT in the rats with oxaliplatin-induced neuropathic pain.All of the three kinds of opioid receptors expression were increased in two venlafaxine groups but in saline group. Conclusion Enlafaxine antagonizes oxaliplatin-induced neuropathic pain through up-regulation of μ，κ and δ opioid receptor.