SUMMARYBioluminescence tomography (BLT) allows in vivo localization and quantification of bioluminescent sources inside a small animal to reveal various molecular and cellular activities. In this paper, the overlap domain decomposition method (ODDM) of BLT is proposed, which refers to divide and conquer techniques for solving BLT by iteratively solving sub-problems on smaller sub-domains. Here, two triangulations of the region are adopted. We can obtain the photon density distribution on the object surface, as well as reconstruct the position of the light source by using ODDM and genetic algorithm. The numerical simulations have shown that ODDM is computationally efficient and fairly robust.