Objective To detect the role of PAR2-PKA/ PKCε signaling pathway in periphery neurons in the transition from acute to chronic pain, and investigate the possible approach to prevent both acute and chronic pain simultaneously. Methods SD rats were randomly divided into control group, sham model group, model group, iPAR2-1 group and iPAR2-2 group. The hyperalgesia priming model was established by injection of carrageenan and PGE2 into the left hindpaw except control and sham model group. PGE2 was administrated at 7 days after carrageenan injection. The PAR2 inhibitor was administrated before and after PGE2 injection separately in the iPAR2-1 group and iPAR2-2 group. The paw withdrawal thresholds (PWTs) of rats in each group was detected before and at 5 h, 3 d, 6 d, 7 d 0.5 h, 7 d 4 h, 7 d 24 h after carrageenan injection. The expression level of PAR2, PKA and PKCε proteins in the dorsal root ganglion (DRG) were detected at 24 h after carrageenan injection. Results The hyperalgesia priming model was successfully generated. When PGE2 was administrated at 7 days after carrageenan injection, the hyperalgesia induced by PGE2 was significantly prolonged. The PWTs of rats in the model group were significantly lower than that of the control and sham model groups ( P <0.01), though the PWTs of sham model group had no significant difference with the control on 7 d 24 h after carrageenan injection ( P >0.05). The expression level of PAR2 and PKCε in the ipsilateral DRG neurons were significantly increased on 7 d 24 h after carrageenan injection, when compared with the control and sham model groups ( P <0.05). PAR2 inhibitor prevented the prolonged hyperalgesia induced by PGE2 ( P <0.05) and decreased the PKCε expression in DRG neurons whenever it was given ( P <0.05). However, PAR2 inhibitor did not regulate the acute inflammatory pain of PGE2 and the expression of PKA in DRG neurons ( P >0.05). Conclusions Inhibition of the expression of PAR2 can prevent the transition from acute to chronic pain. This effect may be related with the inhibitory effect on the activation of PAR2-PKCε signaling pathway in DRG neurons. However, inhibition of PAR2 can not regulate the acute pain. These may because of that the PAR2-PKA signaling pathway does not play a role in acute pain.