Objective The aim of the present study is to verify the ATP-induced varied responses in isolated dorsal root ganglion (DRG) neurons of the adult rat, and investigate the modulatory effects of specific P2X receptor agonist β,γ-me-ATP and protein kinase C (PKC) on P2X receptor-mediated inward current in DRG neurons. Methods Whole cell patch-clamp was employed to record the currents on acutely isolated DRG neurons in the adult rats. Results β,γ-me-ATE similar as ATE evoked 2 distinct subtypes of P2X receptor-mediated inward currents in a dose-dependent manner in DRG neurons. Activation of PKC by phorbol 12,13-dibutyrate (PDBu) significantly inhibited both subtypes of inward currents mediated by P2X receptors in a dose-dependent manner. Conclusion Activation of PKC negatively modulated the P2X receptor-mediated currents in rat DRG neurons, which may be of benefit to preventing the over-excitation of nociceptor under inflammatory or neuropathic conditions.