Bioluminescence tomography (BLT) is an important noninvasive optical molecular imaging modality in preclinical research. To improve the image quality, reconstruction algorithms have to deal with the inherent ill-posedness of BLT inverse problem. The sparse characteristic of bioluminescent sources in spatial distribution has been widely explored in BLT and many L 1 -regularized methods have been investigated due to the sparsity-inducing properties of L 1 norm. In this paper, we present a reconstruction method based on L 1=2 regularization to enhance sparsity of BLT solution and solve the nonconvex L 1=2 norm problem by converting it to a series of weighted L1 homotopy minimization problems with iteratively updated weights. To assess the performance of the proposed reconstruction algorithm, simulations on a heterogeneous mouse model are designed to compare it with three representative sparse reconstruction algorithms, including the weighted interior-point, L1 homotopy, and the Stagewise Orthogonal Matching Pursuit algorithm. Simulation results show that the proposed method yield stable reconstruction results under di®erent noise levels. Quantitative comparison results demonstrate that the proposed algorithm outperforms the competitor algorithms in location accuracy, multiple-source resolving and image quality.