To evaluate the acute to chronic effects of crude oil exposure on hematological and blood biochemical toxicities, Sprague-Dawley rats were given oral doses of 0, 50, or 100 mg/kg BW/day of Iranian heavy crude oil for a period of four weeks. In the acute phase of exposure (one day after four weeks of 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, no significant differences were observed among the experimental groups. In the subchronic and chronic phase of exposure (two months and six months after four weeks of oil treatment), the changes of biomarkers were normalized, except the indicators of oxidative stress. Our findings showed that the bioassay on the indicators of oxidative stress is a sensitive method for determining exposure to crude oil in rats.