Objective To analyze the effect of intrathecal injection of dexmedetomidine on the behavioral activity, pain degree and expression of protein kinase C in spinal dorsal horn of rat models of chronic neuropathic pain, and to investigate the analgesic mechanism of dexmedetomidine. Methods 75 healthy male rats were randomly divided into observation group, model group and control group, 25 rats in each group. Chronic sciatic nerve injury model was established in the observation group and model group. After modeling, intrathecal dexmedetomidine intervention was used in the observation group. The model group was treated with saline injection and there was no intervention in the control group. Before the modeling (BM)and at 3(D3), 5(D5), 7(D7), and 14 (D14)days after medicine administration, the behavioral capacity was evaluated by cumulative evaluation method and movement function evaluation, and the assessment of pain degree (mechanical withdrawal method and thermal withdrawal latency pain threshold detection method), PKC staining score (immunohistochemical SABC method), PKC mRNA assay (RT-PCR method) and PKC protein expression (Western blot) were conducted and the data were statistically analyzed. Results ① Before modeling, the behavior, the cumulative scores of motor function, MWT, and TWL showed no significant differences between the different groups (P>0.05). After modeling, the model group and observation group showed that the cumulative scores and motor function scores were increased significantly, MWT and TWL decreased significantly, and the changes in the observation group were significantly lower than those in the model group (P<0.05). After modeling, the cumulative scores, motor function scores, MWT, and TWL were significantly different between the groups (P<0.05). ② The expression of PKC was negative in the control group and positive in the model group. In the observation group, after the initial establishment of model, the PKC was strongly positive, and along with the prolonged treatment, the PKC expression intensity was decreased, and only weakly positively expressed at 14 d. ③ After modeling, the observation group and model group showed that the PKC mRNA and PKC protein expression levels were significantly higher than that of the control group (P<0.05). With the continuous drug administration, the PKC mRNA and PKC in the observation group were decreasing, and reached a level close to that of the control group at 14 d of drug administration. From the third day after modeling, at the same time points, the amount of PKC expression in the observation group was significantly lower than that in the model group (P<0.05). Conclusions Intrathecal injection of dexmedetomidine can improve the behavior of rat models with chronic neuropathic pain, and reduce the degree of pain. It may be related to the inhibition of protein kinase C expression in the spinal dorsal horn.