Background and purpose: Although we demonstrated willed movement (WM) therapy can facilitate the patients actively participating in the physical activities by cognitive and perceptual stimulation in our previous study, the molecular mechanisms of the willed movement on the patients remains unclear. We initially established the model of WM intervention for rats and identified possible effects of willed movement on motor recovery and on expression of Kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in ischemia core (IC) and ischemia penumbra (IP) regions of rats after cerebral ischemia reperfusion. Methods: Seventy-two adult male Sprague Dawley rats after successful 120-min period of occlusion of the left middle cerebral artery were selected and randomly divided into three groups: middle cerebral artery occlusion (MCAO), WM and environmental modification (EM). Neurological and neurobehavioral assessments were performed and the rats were killed at various recirculation times after MCAO. Reverse transcription-PCR were used to detect mRNA of GluR-GluR4 subunit of AMPA receptors in the areas of IC and IP in all adult rats. Results: Rats following WM intervention showed significantly better acquisition of climbing (every time point tested), forelimb mobility and neurological functions at subacute stage of MCAO. No difference was found in the expression levels of GluR1-GluR4 mRNA among three groups in IC region. However, GluR1 and GluR4 mRNA of rats in group WM were significantly upregulated as compared with rats in group MCAO and group EM in IP region at subacute stage. Conclusions: Early willed movement treatment can increase the expression level of AMPA receptor subunits and thus might increase synaptic transmission and enhance brain plasticity after focal brain ischemia at the subacute stage. (c) 2007 Elsevier B.V. All rights reserved.