The development of Bioluminescence Tomography (BLT) has allowed the quantitative three dimension (3D) whole body imaging and non-invasive study of biological behavior of cancer. However, the ill-posed problem of BLT reconstruction limits the quality of reconstruction result. In this work, we proposed a Bilateral Weight Laplace (BWL) method that utilizes a non-local Laplace regularization to improve the imaging quality of bioluminescence tomography reconstruction. The non-local Laplace regularization was constructed by spatial weight and range weight to penalize the neighborhood-variance of reconstructed source density in both spatial and range domain. To evaluate the performance of BWL method, both dual-source BLT reconstruction experiment in simulation data and in vivo BLT reconstruction in orthotopic glioma mouse model were designed. Furthermore, fast iterative shrinkage/threshold (FIST) method and Laplace method were utilized to compare with BWL. Both dual-source experiment and in vivo experiment demonstrate that the construction results of BWL method provide more accurate tumor position (BCE = 0.37mm in dual-source experiment) and better tumor morphological information