With the development of molecular marker technique and optical imaging technique, In Vivo bioluminescent imaging attracts more and more attention and is extensively used to non-invasively visualize the physiological and pathological process of biological tissues in real time. The photon propagation model and photon propagation rule are two key components of bioluminescent imaging. In this paper, a photon propagation model of bioluminescent imaging based on Monte Carlo method is proposed. With known quantities (e.g. parameters of bioluminescent source, biological tissue, and CCD detectors) and Monte Carlo technique, two mathematic models including photon generation from bioluminescent sources and photon propagation in biological tissue are realized. Then, several comparative experiments are performed and experimental results are given, which illustrates the correctness and efficiency of this algorithm.