Clonidine, an α₂-adrenergic receptor agonist not only induces analgesia but also prolongs the effects of local anesthetic substances. In the present study the effects of clonidine on spontaneous and formalin-induced electrical activity from dorsal skin nerve were investigated. The results showed that clonidine (0.5 mM) decreased the formalin effect on electrical nerve activity whereas clonidine (5 mM) increased it. Co-administration of clonidine (0.5 mM) and lidocaine (0.5 mM) in the presence of formalin decreased the electrical nerve activity. Co-administration of clonidine (5 mM) and lidocaine (0.5 mM + formalin 0.2%) increased nerve activity. In conclusion, clonidine at low concentration (0.5 mM) exhibited mild anesthetic effect and also potentiated the anesthetic effect of lidocaine whereas in high dose (5 mM) showed opposite effect.