With　the　popularization　of　biomechanical　simulation　technology,　aiming　at　the　rehabilitation　of　ankle　joint　injury,　we　imported　simplified　model　of　proposed　2-UPS/RR　(two　identical　unconstraint　kinematic　branches　with　a　universal–prismatic–spherical　(UPS)　structure　and　two　rotating　pair　(R))　ankle　rehabilitation　robot　into　AnyBody　Modeling　System.　Therefore,　a　human–machine　model　was　established　using　the　HILL-type　muscle　model　and　muscle　recruitment　criteria.　This　paper　investigated　the　effects　of　rehabilitation　trajectories　on　biomechanical　response　during　rehabilitation.　Additionally,　three　main　lower　limb　muscles　(soleus,　peroneal　brevis,　and　extensor　digitorum　longus)　were　examined　under　different　rehabilitation　trajectories　(plantar　dorsiflexion,　varus　or　valgus,　and　compound　movement)　in　the　present　study.　Based　on　the　biomechanical　response　of　lower　limbs,　the　results　showed　that　different　muscles　had　different　sensitivities　to　the　change　of　rehabilitation　trajectories.　The　correlation　coefficient　between　joint　force　and　plantar　dorsiflexion　angle　reached　0.99　(P　＜　0.01),　indicating　that　the　change　of　joint　force　was　mainly　dominated　by　plantar　dorsiflexion/plantar　flexion,　but　also　affected　by　varus　or　valgus.　Safe　rehabilitation　training　can　be　achieved　by　controlling　the　designed　2-UPS/RR　rehabilitation　robot.　The　behavior　of　muscle　force　and　joint　force　under　different　rehabilitation　trajectories　can　meet　the　needs　of　rehabilitation　and　treatment　of　joint　diseases,　and　provide　more　reasonable　suggestions　for　early　rehabilitation.　Graphical　Abstract:　[Figure　not　available:　see　fulltext.]　©　2022,　International　Federation　for　Medical　and　Biological　Engineering.