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 motion capture system and a force platform were used to collect the lower limb kinematic data and the ground reaction force during walking that were used as input parameters to simulate the lower limb muscle activation and knee joint forces. Results The results from the musculoskeletal model are consistent with the results by the inverse dynamics based on the three-dimensional motion capture system. The patient's rectus femoris is activated in the loading response and mid stance phases, different from healthy subjects. The activation timing and amplitude of the quadriceps muscle in the three patients was significantly different before and after TKA. The patient's peak joint forces before TKA were 2.95, 3.15 and 3.43 times of body weight with the constant load of more than 2 times of body weight during stand phase. The peak joint force after TKA were 2.09, 2.48 and 3.96 times of body weight respectively. The joint force was not improved and the knee function did not reach the normal level six months after TKA. Conclusion The results of the musculoskeletal model in this study have certain reliability, this model can provide a biomechanical auxiliary method for total knee replacement surgery in the future.