The expression of long-lasting synaptic plasticity requires synthesis of new proteins. A critical locus for protein synthesis to support synaptic plasticity is the dendrites. Previous studies demonstrate that synaptic activity activates dendritic protein synthesis. The mechanism by which synaptic activity stimulates protein synthesis in dendrites is, however, poorly understood. This study is to determine the role of the mitogen-activated protein kinase signaling pathway in activity-dependent dendritic protein synthesis. Using a green fluorescent protein reporter with CaMKII 5' and 3'untranslated regions, we show that dendritic synthesis of the green fluorescent protein induced by N-methyl-D-aspartate stimulation is abolished by U0126, a specific inhibitor of mitogen-activated protein kinase signaling. Our results suggest an important role of the mitogen-activated protein kinase signaling in dendritic protein synthesis induced by N-methyl-D-aspartate receptor activation.