Abstract: Objective To investigate the analgesic effect of dexmedetomidine (Dex) on oxaliplatin-induced neuropathic pain in rats and explore its mechanism. Methods SD rats were randomly divided into control, model, Dextreatment, and Dex + atipamezole groups. In the latter 3 groups, rat models of neuropathic pain were established by a single intraperitoneal injection of oxaliplatin. The paw withdrawal threshold (PWT) to mechanical stimuli and tail withdrawal latency (TWL) to thermal stimuli of the rats were determined. Western blotting and immunofluorescence assay were performed to observe the expression of spinal phosphorylated STAT3 (p-STAT3) in the rats. Results Compared with the rats in the control group, the rats in the model group and Dex+atipamezole group showed significantly decreased PWT and TWL (cold) and increased expression of p-STAT3 in the spinal cord (P<0.05). In Dex group, PWT and TWL (cold) were significantly increased (P<0.05) and p-STAT3 expression in the spinal cord was significantly decreased (P<0.01) 60 to 120 after Dex treatment as compared with those in the model group, and these effects of Dex were significantly attenuated by the administration of atipamezole (P<0.05). Conclusion Dex can alleviate oxaliplatin-induced neuropathic pain in rats by inhibiting the phosphorylation of STAT3 in the spinal cord.