Posttraumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA) resulting from the integrated outcome of joint injury, accounting for more than 12% of the overall OA cases. Although current therapies restore joint kinematics and alleviate inflammation, more than 20% patients undergo the unexpected progression of PTOA. Exercise is widely recommended to patients with OA and treadmill training is effective in preventing osteoarthritic changes in PTOA animals. However, the understanding gap of modified treadmill exercise models with different exercise dose and loading weight still exists. To evaluate the effects of body weight-supported treadmill training on PTOA, 30 rats were divided into the sham group (n = 6) and the PTOA group (n = 24) which were further assigned into three subgroups including the sedentary, the treadmill walking (TW), and the body weight-supported treadmill training (BWSTT) groups. The training groups were subjected to 4-week treadmill training at the speed of 15 m/min for 30 min/d, 5 d/wk. Then the tibias were elevated by histological staining, immunohistochemical staining, and micro-computed tomography. In our results, the significant OA-relevant changes in cartilage-subchondral bone unit were observed in the PTOA groups after surgery, characterized by cartilage degradation and subchondral bone remodeling. After 4-week treadmill training, the OA-relevant changes in cartilage-subchondral bone unit were alleviated and BWSTT is more efficient to maintain cartilage integrity and attenuate the subchondral bone loss and remodeling than TW. In conclusion, BWSTT is a promising and favorable treatment of PTOA slowing down the development of PTOA by reprogramming the cartilage-subchondral unit.