Since I-125 emits low energy (27-35 keV) radiation, thinner crystal and collimator could be employed and, hence, it is favorable to obtain high quality images. The purpose of this study was to derive the optimized parameters of I-125 SPECT using a new simulation tool, GATE (Geant4 Application for Tomographic Emission). Materials and Methods: To validate the simulation method, gamma camera developed by Weisenberger et al. was modeled. NaI(Tl) plate crystal was used and its thickness was determined by calculating detection efficiency. Spatial resolution and sensitivity curves were estimated by changing variable parameters for parallel-hole and pinhole collimator. Performances of I-125 SPECT equipped with the optimal collimator were also estimated. Results: In the validation study, simulations were found to agree well with experimental measurements in spatial resolution (4%) and sensitivity (3%). In order to acquire 98% gamma ray detection efficiency, NaI(Tl) thickness was determined to be 1 mm. Hole diameter (mm), length (mm) and shape were chosen to be 0.2:5:square and 0.5:10:hexagonal for high resolution (HR) and general purpose (GP) parallel-hole collimator, respectively. Hole diameter, channel height and acceptance angle of pinhole (PH) collimator were determined to be 0.25 mm, 0.1 mm and 90 degree. The spatial resolutions of reconstructed image of the I-125 SPECT employing HR:GP:PH were 1.2:1.7:0.8 mm. The sensitivities of HR:GP:PH were 39.7:71.9:5.5 cps/MBq. Conclusion: The optimal crystal and collimator parameters for I-125 imaging were derived by simulation using GATE. The results indicate that excellent resolution and sensitivity imaging is feasible using I-125 SPECT.