Spinal cord injury (SCI) can promote profound functional modification in various brain centers. However, the question of whether SCI can affect the generation of silent synapses that regulate neuronal plasticity in the hippocampus remains unclear. In the present studies, we demonstrated that acute SCI diminished silent synapses in hippocampus of lesioned rats. Furthermore, the SCI induced decline in silent synapses appeared to require the activation of NR2B-containing N-methyl-D-aspartate receptors. Our data show that SCI impaired synaptic plasticity in the hippocampus, suggesting that this region may serve as a potential therapeutic target for meliorating impaired brain functions after SCI.