Due to spatial disorientation reported in space, spatial memory and navigation performances could be more largely impaired by gravity changes. Hippocampus, a key structure for spatial memory, receives inputs from gravity-sensing otolith organs. To determine the key molecules in the rat hippocampus that contribute to an adaptation to altered gravity in terms of spatial memory performance. Gene expression of hippocampus and spatial memory after continuous two-weeks exposure to 2 G hypergravity (HG) were examined using a microarray analysis followed by real-time PCR methods and radial arm maze testing, respectively. Serum cortisol levels during HG load were measured as a stress marker. Accuracy to enter the correct arms in HG rats was significantly lower than that of controls, indicating an impaired spatial memory due to gravity changes. Microarray analysis followed by real-time PCR confirmed an upregulation of insulin like growth factor binding protein 2 (IGFBP2) gene. Serum cortisol level was the same level as controls at the last day of hypergravity, suggesting the adaptation to HG-induced stress. Given that the IGF systems are involved in neurotrophic and synaptic plasticity mechanisms, IGF system might contribute to the adaptation to altered gravity in terms of spatial memory.