Abstract: A highresolution and low-cost small animal single photon emission computed tomography (SPECT) system was designed based on a clinical scanner and a pinhole collimator. Optimal design schemes of a single-pinhole collimator and a seven-pinhole one were proposed, in terms of achieving the best trade-off of field of view size, spatial resolution and sensitivity. System performances of the two design schemes were compared by evaluating the average spatial resolution and sensitivity over the full field of view, and the seven-pinhole collimator design demonstrated improved resolution and better sensitivity. Monte Carlo simulation studies validate that ultra-high 0.5 mm spatial resolution can be achieved with the proposed seven-pinhole design, which is cost-effective comparing to the existing animal SPECT systems equipped with dedicated detector.