This study evaluated the expression of phosphorylated signal-regulated kinase1/2 (pERK1/2), which is one of the main factors regulating transcription of the cfos oncogene in neurons, in the vestibular nuclei of Sprague-Dawley rats following unilateral labyrinthectomy (UL). Surgical UL was performed to eliminate afferent signals from the peripheral vestibular receptors in the inner ear, under a surgical microscope, 2 hours after anesthesia. Significant numbers of pERK1/2 immunoreactive neurons were seen in the superior, medial, and inferior vestibular nuclei. There were more pERK1/2 immunoreactive cells in the vestibular nuclei contralateral than in the vestibular nuclei ipsilateral to the injured labyrinth, which resulted in significant asymmetric expression of pERK1/2 immunoreactive cells. Subsequently, the pERK1/2 immunoreactivity decreased rapidly, disappearing 90 min after labyrinthectomy. No pERK1/2 labeling was seen in the lateral vestibular nucleus. These results suggest that intracellular signal pathways for the activation of extracellular signal-regulated kinase in the vestibular nuclei are involved in lesion-neural plasticity in the vestibular system.