Objective To investigate the activation of extracellular signalregulated kinase (ERK) an d cAMPresponsive element binding protein (CREB) in the anterior cingulate cortex (ACC) induced by peripheral injection of formalin. Methods 5% formalin was injected subcutaneously into the unilateral hindpaw. The rats w BR>ere perfused or killed and the ACC dissected at different time points. The activation of phosphorylated ERK (pERK) and phosphorylated CREB (pCREB) in the ACC we are observed by immunohistochemical and Western blotting techniques. Results Subcutaneous injection of formalin induced the activation of pCREB and pERK in the ACC. Formalininduced the activation of pERK and pCREB in the ACC peaked at 3 min and 30 min after stimulation, respectively. The total ERK and CREB had no significant changes. Conclusion The ACC could receive peripheral noxious information and the ERK and CREB in the BR>ACC might involve in the processing of the primary unpleasentn