Monocular deprivation (MD) of vision leads to a loss of cortical response to the deprived eye in the early postnatal period (ocular dominance plasticity). The activity of several signal molecules, including extracellular signal-regulated kinase (ERK), has been reported as playing a crucial role in the ocular dominance plasticity. Although pharmacological inhibition of ERK disturbed the ocular dominance plasticity, it remains to be elucidated how the ERK activity is modulated by MD. We herein report the effects of MD on ERK activation in the visual cortex of young and adult rats. Phosphorylated ERK (pERK)-immunopositive cells are mainly distributed in layers II/III of the visual cortex. Following MD, we found a significant decrease in the density of pERK-immunopositive cells in the cortex receiving deprived-eye inputs in both young and adult animals. The amount of pERK protein also decreased in the input-deprived cortex as revealed by Western blotting. Regarding the subcellular localization of pERK, we found a significant increase in the pERK-immunopositive nucleus following MD in young animals. In these animals, the amount of pERK protein in the nuclear fraction of cortical tissue was significantly increased. No up-regulation of the nuclear pERK was observed in adults or following binocular deprivation. These findings suggest that ERK activation may therefore be regulated by different mechanisms between young and adult animals, and MD during the developing period may thus specifically up-regulate the nuclear signalling of ERK.