The aim of this study was to histopathologically assess the toxic effect of desflurane on the liver and the kidney. The rats (n = 150) were grouped into five main and three subgroups according to the exposure time to the anesthetic agent. The first group was planned as 1 MAC Desflurane+N(2)O+O(2), the second group as 1 MAC Desflurane+O(2), the third group as 2 MAC Desflurane+N(2)O+O(2), the fourth group as 2 MAC Desflurane+O(2) and the 5th group as the control group. Each group was given the anesthetic agent for 1, 3 or 6 h. The rats that were exposed to the anesthetic agent with an adequate dose and for an adequate period of time were sacrificed properly. Livers and kidneys were resected and examined by light microscopes following the routine tissue follow-up procedures. Significant histopathological changes were observed in all groups compared to the control group. However, the pathological findings of the group 2 MAC Desflurane+N(2)O+O(2) at the 6th h with the light microscope was significantly more than those of other groups at all times. It was concluded that although, desflurane caused cellular changes in liver and kidney tissue, it did not cause any clinical changes. Nevertheless, further studies are required to support this opinion.