The　mechanical　adaptive　responses　of　bone　are　affected　by　various　parameters　of　the　loading,　such　as　magnitude,　rate,　frequency,　number　of　cycles,　and　recovery　time.　However,　the　precise　relationships　between　different　loading　parameters　and　bone　adaptation　as　well　as　their　governing　mechanism　remain　unclear.　Here,　we　developed　a　novel　multi-scale　model　of　whole　bone-lacunocanalicular　network　(LCN)-osteocyte　characterizing　whole-bone　deformation-produced　fluid　flow　within　a　large　LCN　as　well　as　responses　of　osteocytes　to　fluid　shear　stress　(FSS)　via　opening,　closing,　or　inactivating　mechanosensitive　ion　channels　(MSIC).　The　model　was　next　used　to　examine　the　effects　of　loading　magnitude,　frequency,　cycle　numbers,　and　recovery　time　on　the　responses　of　osteocytes.　Results　showed　that　the　load　magnitude　and　frequency　mainly　affected　the　proportion　of　open　MSIC　by　changing　FSS　on　the　osteocytes.　When　the　load-induced　FSS　increased,　the　proportion　of　open　osteocyte　MSIC　was　enhanced.　With　an　increase　in　the　cycle　number,　MSIC　transformed　gradually　from　an　open　state　into　an　inactivated　state,　resulting　in　saturation　in　response　to　continuous　FSS.　Interestingly,　a　short-term　recovery　time　restored　the　MSIC　to　a　closed　state　which　could　turn　into　an　open　state　following　subsequent　loading,　while　a　long-term　recovery　time　was　helpful　for　recovering　the　mechanical　sensitivity　of　the　osteocytes.　These　computational　results　largely　replicated　the　mechanical　responses　of　bone　as　observed　in　in　vivo　animal　loading　experiments,　suggesting　the　importance　of　osteocyte　MSIC　in　response　to　different　loading　parameters.　This　multiscale　model　considering　osteocyte　MSIC　could　provide　mechanistic　insights　into　bone　adaptation　to　distinct　mechanical　stimuli.