Abstract: This study was performed to determine the probable effects of Buprenorphine and Methadone on brain volume of male rats. In this study 15 Wistar male rats were selected and divided into three groups randomly (n = 5).The first group was administrated 0.5 mg kg-1 methadone intraperitonealy for 15 days. Second group was administrated 30 ng buprenorphine intraperitonealy for 15 days. No injection was done on controls. Soon after the last injection, the animals were anaesthetized deeply, and then the brain dissected carefully and put in 7% buffered formaline solution. Following fixation brains were embedded in 3.5% agar and 1 mm coronal slices were prepared by means of a tissue slicer . Afterward using Cavalieri's principles, the volumes of the brains were calculated by point counting. Results were not showed any significant changes in volume of rat's brain following methadone and buprenarphine administration on the brain volume in rats.