We investigated the signal pathway related to induction of Nurr1, transcription factor, by cAMP in neuroblastoma N2A and C6 glioma cell lines. Nurr1 expression was induced by forskolin, an adenylate cyclase activator, via activation of CREB in both N2A and C6 cells. The effect of forskolin on ERK, however, was cell specific. ERK phosphorylation was stimulated by forskolin in N2A cells whereas it was inhibited in C6 cells. Pretreatment with H89, a PKA inhibitor, blocked the forskolin-induced Nurr1 expression in both N2A and C6 cells. Interestingly, pretreatment with PD98059, an MEK inhibitor, showed differential effects. Pretreatment with PD98059 inhibited the forskolin-induced Nurr1 expression in N2A cells, however, in C6 cells, Nurr1 expression was further increased. Our results suggest that ERK pathway plays a differential role in cAMP-induced Nurr1 expression in N2A and C6 cells.