Abstract: In order to minimize the penetration and scattering effect of gamma ray on the pinhole collimator, Monte-Carlo simulation was utilized to optimize the designs of pinhole collimator for a single photon emission computed tomography (SPECT) system. The simulated results are in good agreement with the experimental data of the system performances in both sensitivity and spatial resolution, which indicates that the optimized designs of the pinhole collimator are satisfied well with the requirements of high-resolution SPECT for small animal imaging.