The present study investigated the role of peripheral P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out on male Sprague- Dawley rats weighing 220 to 280 g. Formalin (5%, 50 μL) and complete Freund's adjuvant (CFA, 25 μL) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. TNP-ATP, a P2X2,2/3,4 receptor antagonist, or OX-ATP, a P2X7 receptor antagonist, was then injected subcutaneously at 20 minutes prior to formalin injection. One of the antagonists was administered subcutaneously at three days after CFA injection. The subcutaneous injection of formalin produced a biphasic nociceptive behavioral response. Subcutaneous pretreatment with TNP-ATP (80, 160 or 240 μg) significantly suppressed the number of scratches in the second phase produced by formalin injection. The subcutaneous injection of 50 μg of OX-ATP also produced significant antinociceptive effects in the second phase. Subcutaneous injections of CFA produced increases in mechanical and thermal hypersensitivity. Both TNP-ATP (480 μg) and OX-ATP (100 μg) produced an attenuation of mechanical hypersensitivity. However, no change was observed in thermal hypersensitivity after the injection of either chemical. These results suggest that the blockade of peripheral P2X receptors is a potential therapeutic approach to the onset of inflammatory pain in the orofacial area.