Abstract: Forty Sprage-Dawely rats of both sexes (4 to 5 months of age) were used in this experiment. Formalin solution was provided with drinking water ad libitum for 8-12 weeks. Fourteen rats received a daily dose of 80 mg/kg/day, 13 rats received 150 mg kg ¹ day while another 13 rats were given tap water. Animals weights, food and water consumption were monitored throughout the experiment. The concentration of the test substance in the solutions were adjusted weekly on the basis of mean body weight and liquid consumption to maintain a target intake of 80 and 150 mg/kg/day throughout the experiment. Arterial blood after eight weeks were collected from hypnotized rats given Midazolan-3 mg kg ¹ intra-peritoneally (Dormicum F. Hoffmann-La Roche, Ltd, Switzerland, 2371081). Animals became partially anesthetized and blood was collected by cardiac puncture from the left ventricle. Standard procedure was followed to store the blood and immediately transported to the laboratory. The samples were analyzed with blood gas analyzer (Omni 4: AVL, Graz., Austria 2493) pH, HCO₃ , PO₂, PCO₂, O₂ Saturation, BE (Base Excess). The same procedure and parameters were followed and tested after 12 weeks of exposure with the blood collected from the tip of the tail of unanesthetized rats. Besides, blood samples were collected for reticulocytes counts and stained with retic stain (brilliant cresyl blue). Liver and kidney were excised and weighed and the relative organ weights were calculated. Histological examinations were performed on kidney and liver after routinely processed for normal histological procedure. Sections were stained with hematoxylin and eosin stain. Body weight, food and water consumption showed a dose related decrease which were reflected on the general animal health. There were no clear statistical differences between treated and control groups in respect to most blood gases parameters used with the exception of the pH and PCO₂. A significant decrease in pH and PCO₂ in rats ingested 150 mg/kg/day formalin solution for 12 weeks were evident. Liver and kidneys showed no histological changes in treated rats of all groups. It was observed that reticulocytes percentage decreased significantly in a non-dose related manner. In conclusion, the effect of the exposure to formalin differ from species to species and from system to system according to the availability, activity and amount of the enzyme formaldehyde dehydrogenase present in that specific species or system.