As　a　promising　optical　molecular　imaging　modality,　bioluminescence　tomography　(BLT)　has　attracted　remarkable　attention　for　its　excellent　performance　and　high　cost-effectiveness,　which　can　be　employed　to　speciffically　and　directly　reveal　physiological　and　pathological　activities　in　vivo　at　molecular　and　cellular　levels.　The　goal　of　BLT　is　to　reconstruct　the　internal　bioluminescent　light　source　with　surface　measurements.　Therefore,　the　calculation　of　surface　light　exitance　plays　an　important　role　in　the　inverse　source　reconstruction,　whereas　photon　propagation　is　complicated　because　of　strongly　scattering　property　of　the　biological　tissue.　In　this　contribution,　a　novel　meshless　local　Petrov-Galerkin　(MLPG)　method　based　on　diffusion　approximation　model　is　developed　to　avoid　the　complex　and　time-consuming　mesh　division　in　the　conventional　finite　element　method　(FEM),　and　MLPG　requires　only　a　series　of　discretized　nodes　without　consideration　of　element　information　and　node　connectivity.　Compared　with　other　meshless　methods　based　on　global　weak-form,　background　cells　used　for　Gauss　quadrature　are　also　omitted　in　the　proposed　method.　In　addition,　the　tissue　optical　parameters　are　incorporated　as　a　priori　knowledge　in　this　algorithm.　Finally,　the　performance　of　this　method　is　valuated　using　two-　and　three-dimensional　numerical　simulation　experiments.　The　results　demonstrate　the　effectiveness　and　feasibility　of　the　presented　algorithm　to　predict　boundary　bioluminescent　light　power　distribution.　©　2009　SPIE.