Isane was part of the reinforcements sent to Hueco Mundo in order to assist Ichigo and his friends. She and Unohana healed Chad and Gantenbainne Mosqueda after saving them from the Exequias. After Unohana headed to Fake Karakura Town, she ordered Isane to assist Captain Byakuya Kuchiki and Captain Kenpachi Zaraki in battle against Espada Yammy Llargo. During the Wandenreich invasion of Soul Society, Isane and the rest of the 4th Division were ordered by Yamamoto to remain in their barracks.