To evaluate the acute to chronic effects of crude oil exposure on hematological and blood biochemical toxicities, Sprague-Dawley rats were given by oral doses of 0, 50 or 100 mg/kg BW/day of Iranian heavy crude oils for four weeks. In the acute phase of exposure (1 day after 4 weeks oil treatment), decreases in weight of thymus, serum level of interferon gamma (IFN-γ), superoxide dismutase (SOD) and catalase activities in liver or kidney, and increase in weight of adrenal gland occurred after oral administration of crude oil. In body weight, histopathological examination, hematological and blood biochemical analyses in the acute phase of exposure, there were no significant differences among the experimental groups. In the subchronic and chronic phase of exposure (2 months and 6 months after 4 weeks oil treatment), the changes of biomarkers were normalized except the indicators of oxidative stress. Our findings show that the bioassay on the indicators of oxidative stress is a sensitive method for determining exposure to crude oil in rat.