Abstract: Twenty-six patients with flexible flatfoot were tested before and after fatigue at a speed of (3.0 ± 0.3) m/s in a 10 m experimental field. Pedar-x system and insoles were used to measure the plantar pressure of eight areas of the flatfoot before and after fatigue when running with orthopedic insoles and flat insoles. Compared with the flat insole, the orthopedic insole significantly reduced the peak force, peak pressure and force-time integral of the heel of the flatfoot when running. Compared with before fatigue, the peak force in the medial forefoot and heel area and the peak pressure in the medial forefoot and medial midfoot area increased significantly when the patients wore flat insoles after fatigue. However, there was no significant difference in these indexes above the orthopedic insole. Orthopedic insoles are helpful to reduce the risk of foot injury caused by running fatigue of flatfoot and realize healthy running.