This study aims to perform an in vivo investigation evaluating the injury to the pancreas and adjacent tissue of swine resulting with high-intensity focused ultrasound (HIFU) combined with radiotherapy (RT). The protocol was approved by the animal ethics committee at the Peking University First Hospital. A total of 12 domestic swine were divided into four groups: control, HIFU only, RT only and HIFU + RT. The injury to the pancreas, adjacent tissue and tissue within the acoustic path of the HIFU beam was assessed based on gross and histologic findings. For the targeted region of the pancreas, the score of the combined group was higher than that of the HIFU group and there was significant difference. For the acoustic path tissue, there was no significant difference except between the control group and the other groups. HIFU combined with RT increased the injury to the targeted pancreas, without increased injury to tissue outside of the targeted region. (E-mail: xsgao777@hotmail.com) (C) 2011 Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.