This study evaluated whether the administration of a NSAID, sodium diclofenac, can promote alterations in the expression of Fos protein in central amygdala (CEA) and the lateral hypothalamus (LH) after 6 h of experimental tooth movement with a controlled force of 70 g, applied to the superior central incisors of rats. Adult male rats were anesthetized and divided into four groups: Control, no orthodontic appliance (OA); OA activated with 70 g; OA activated with 70 g and pretreated with diclofenac sodium (5 mg/kg, intramuscular); and diclofenac sodium alone. Six hours after the onset of the experiment the rats were reanesthetized and perfused with 4% paraformaldehyde. The brains were removed and fixed, and sections containing the CEA and LH were processed for Fos protein immunohistochemistry. The results show that in the control group, intramuscular injection of a ketamine/xylazine mixture did not induce IR-Fos cells in the CEA or LH. However, in the 70 g group, IR-Fos was the strongest observed (P < 0.05, Newman-Keuls) in the CEA and LH compared with the other groups. Furthermore, pretreatment with sodium diclofenac reduced IR-Fos in these regions. Pretreatment with diclofenac sodium reduced Fos protein immunoreactivity in the CEA and LH induced by orthodontic force application. The expression of Fos protein in the CEA and LH is dependent, at least in part, on the inflammatory reaction induced by teeth movement. Diclofenac can be an alternative medication of choice for relief of orthodontic pain.