Bioluminescence　tomography　(BLT)　is　a　molecular　imaging　modality　which　can　three-dimensionally　resolve　the　molecular　processes　in　small　animals　in　vivo.　The　ill-posedness　nature　of　BLT　problem　makes　its　reconstruction　bears　nonunique　solution　and　is　sensitive　to　noise.　In　this　paper,　we　proposed　a　sparse　BLT　reconstruction　algorithm　based　on　semigreedy　method.　To　reduce　the　ill-posedness　and　computational　cost,　the　optimal　permissible　source　region　was　automatically　chosen　by　using　an　iterative　search　tree.　The　proposed　method　obtained　fast　and　stable　source　reconstruction　from　the　whole　body　and　imposed　constraint　without　using　a　regularization　penalty　term.　Numerical　simulations　on　a　mouse　atlas,　and　in　vivo　mouse　experiments　were　conducted　to　validate　the　effectiveness　and　potential　of　the　method.