It is well known that diabetes mellitus may cause neuropsychiatric disorders such as anxiety disorders. Diabetes may also cause reduced IGF-1 (insulin like growth factor-1) levels in brain and blood. The purpose of the present study was to investigate the relationship between diabetes induced anxiety and IGF-1 levels in diabetic rats. The anxiety levels of rats were assessed 2 weeks after intraperitoneal injection of streptozotocin. Diabetic rats had higher levels of anxiety, as they spent more time in closed branches in elevated-plus-maze-test and less time in the center cells of open-field-arena. Prefrontal cortex (PFC) IGF-1 levels and neuron numbers were decreased and apoptosis was increased in diabetic rats. Blood IGF-1 levels decreased in a time dependent fashion following streptozotocin injection while blood corticosterone levels increased. They had higher malondialdehyde levels and lower superoxide dismutase enzyme activity. Oxidative stress may negatively affect blood and PFC tissue IGF-1 levels. Reduction in IGF-1 may cause PFC damage, which may eventually trigger anxiety in diabetic rats. Therapeutic strategies that increase blood and brain tissue IGF-1 levels may be promising to prevent psychiatric sequelae of diabetes mellitus. (C) 2012 Elsevier Ireland Ltd. All rights reserved.