Flat feet associates with altered knee kinematics, kinetics, as well as knee pain. Fatigue of plantar intrinsic foot muscles may increase the navicular drop. However, it is unclear how fatigue influences the knee pain in individuals with flat feet. The purpose of this study was to assess the effect of fatigue on knee kinematics and kinetics in flat feet people during walking. Methods: This is a quasi-experimental research. Ten individuals with flat feet (Mean±SD age: 24.4±2.16 y; Mean±SD height: 177.2±4.31 cm; Mean±SD mass: 81.9±17.4 kg) and 10 normal subjects (Mean±SD age: 25.28±6.33 y; Mean±SD height: 168.61±27.71 cm; Mean±SD mass: 78.13±26.93 kg) were participated in this study. A Vicon motion analysis system (100 Hz) with four cameras and two Kistler force plates (1000 Hz) were used to measure knee kinematics and kinetics during gait before and after fatigue. For between group and within group comparisons, the Independent t test and repeated measures analysis of variance were used, respectively. SPSS (V. 22) was used to analyze data with the significance level of P<0.05. Results: Knee range of motion of flat feet group in frontal plane (9.37±2.54 degree) was significantly higher than that of healthy group (P=0.01) in the pretest. In the flat feet group, the knee moment in sagittal, frontal, and horizontal plan was significantly greater than those in the healthy group by 0.86 (P=0.002), 0.25 (P=0.016) and 0.19 (P=0.000) Nm/BW, respectively in the pretest. Adductor moment increased after fatigue protocol in the healthy group by 0.08 Nm/BW. Conclusion: Before exhaustion, the knee moments in sagittal, frontal, and horizontal planes in the flat feet group were significantly higher than that in the healthy group. In the flat feet group, fatigue resulted in a decrease on the knee flexion and abduction moments and increase in knee ROM in sagittal and frontal plane in the flat foot group. The decreased knee muscle moments may result in an increased loading on the knee joint. It appears that extreme exhausting activity might place the knees of flat feet individuals at the risk of pathology and injury.