The central administration of somatostatin (SMS) in humans became a subject of controversy on the issue of potential neurotoxicity on the spinal cord. The study was aimed at the assessment of the neurodegenerative effects of chronic epidural SMS administration in rabbits. Rabbits were randomly assigned to two groups: the SMS and the control group. The SMS group received 100 mug SMS and the control group received isotonic saline by epidural catheter for 15 consecutive days. Then, laminectomy was performed and the spinal cord was removed. Light and electron microscopic examinations were performed. In the control group, a mild dural inflammatory response and in the SMS group, loss of Nissl bodies at the pericarion, chromatolysis and shrinking at nucleus membranes were observed in all animals at different degrees in light microscopy. In electron microscopy, mitochondrial swellings, irregularities in both nucleus and cell membrane, splitting at myelin lamellae, degeneration at myelin sheath and shrinking of axolemma were found in the SMS group. Our results showed the neurotoxic effects of chronic administration of SMS in rabbits both in light and electron microscopy even in a quite low doses. However, there were no significant clinical findings for the neurological effects during long term follow up.