Distraction　osteogenesis　(DO)　is　a　mechanobiological　process　of　regenerating　bone　tissue　by　tension　stress.　DO　is　used　clinically　to　lengthen　bones　or　to　treat　critical　size　bone　defects.　Although　DO　provides　satisfactory　results　in　many　cases,　the　prolonged　period　of　treatment　remains　a　major　challenge　that　needs　to　be　overcome.　Various　attempts　have　been　devoted　to　accelerating　bone　regeneration　during　DO.　One　common　approach　is　manipulation　of　the　applied　mechanical　loading　by　altering　distraction　strategies.　In　this　article,　we　reviewed　relevant　in　vivo　animal　studies　exploring　the　effects　of　changing　mechanical　environments,　by　varying　distraction　parameters　(e.g.,　rate　and　frequency)　or　adding　compression　loading,　on　bone　regeneration　in　DO.　We　further　presented　how　the　mechanically-regulated　bone　regeneration　process　during　DO　could　be　simulated　by　in　silico　models　incorporating　mechano-regulatory　tissue　differentiation　rules.　A　comprehensive　review　of　those　in　vivo　and　in　silico　studies　may　not　solely　provide　important　references　for　development　of　improved　DO　protocols　in　clinic,　but　also　promote　a　deeper　understanding　of　the　mechanobiological　mechanism　of　bone　regeneration.　©　2021　The　Author(s)