Objective To compare and analyze the lower limb muscle activity and knee joint force during the stance periods of gait cycle in patients with osteoarthritis before and after total knee arthroplasty (TKA). Methods Based on the OpenSim platform, lower extremity musculoskeletal models of one healthy subject and three patients with osteoarthritis before and after TKA were established. A three-dimensional （3D） motion capture system and a force platform were used to collect the lower limb kinematic data and the ground reaction force during walking, which were used as input parameters to simulate the lower limb muscle activation and knee joint forces. Results The results from the musculoskeletal model were consistent with the results by inverse dynamics based on the 3D motion capture system. The patient's rectus femoris was activated in the loading response and mid stance phases, which was different from that of healthy subject. The activation timing and amplitude of the quadriceps muscle in 3 patients were significantly different before and after TKA. The peak joint forces of 3 patients before TKA were 2.95, 3.15 and 3.43 times of body weight (BW) with the constant load of more than 2 times of BW during stand phase. The peak joint force after TKA were 2.09, 2.48 and 3.96 times of BW respectively. The joint force was not improved and the knee function did not reach the normal level six months after TKA. Conclusions The results of the established musculoskeletal model have certain reliability, and this model can provide a biomechanical auxiliary method for TKA surgery in the future.