An animal model of Osteoarthritis (OA) was established to observe the influences of low-intensity pulsed ultrasound (LIPUS) and nano magnet application (NMA) on Collagenase 3 (MMP-13) expression and the activation status of mitogen activated protein kinases (MAPKs) in rabbit. 24 experimental rabbits from New Zealand were randomly divided into four groups: LIPUS, NMA, LIPUS + NMA group, and control group. The experimental rabbit OA model was established in the right knee joint of rabbits received ACLT operation. Rabbits in LIPUS group received LIPUS treatment and rabbits in NMA group were given NMA treatment. In LIPUS + NMA group, both treatments were applied on experimental rabbits everyday. However, the rabbits in control group only underwent ACLT operation. Four weeks later all rabbits were killed and changes of histopathology in rabbit articular cartilage were assessed and evaluated using Mankin method (Modified Mankin Scale). The protein expressions of MMP-13 and MAPKs were estimated using Western Blot. The results showed that both LIPUS and NMA treatments could significantly decrease the Mankin scores and suppress the expression level of MMP-13. However, there were some inverse results of MAPKs expression in these two applications and imply their treatment mechanisms of OA were different from each other.