Objective: Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are important clinical problems in thoracic surgery and critical care medicine. Most of the treatment methods are still supportive. Thymoquinone has anti-inflammatory, spasmolytic, bronchoditator and antibacterial effects. We studied its effects on ALI/ARDS in a rat model. Methods: ALI/ARDS was developed in 40 Sprague-Dawley mate rats (200-250 g in weight) by intratracheal instillation of human gastric juice (pH 1.2). Rats were treated with mechanic ventilator for 3 h. There were five groups: Control group (n = 11); Steroid group (n = 10); Ethanol group (n = 5); Thymoquinone group (n = 9) and Thymoquinone+Steroid group (n = 5). No instillation except gastric juice was applied in the first group. Thymoquinone was given in dosage of 6mg/kg, metilprednisolone in dosage of 10 mg/kg, ethanol 0.75 ml/kgintraperitoneatly (IP). Blood gas analysis and compliance measurement were done. At the end of the third hour, rats were sacrificed and their lungs were excised for histopathotogical examination. Results: In the thymoquinone group, the ratio of arterial oxygen to the fraction of inspired oxygen (PO2/FiO(2),) was significantly better compared to the other groups (P = 0.0000.043). Static compliance measurements revealed higher values in thymoquinone and thymoquinone+steroid groups. Histopathotogical examinations showed that affected lung tissue is tower in groups 2 and 4 (P = 0.000-0.027). Conclusions: This study revealed that thymoquinone improved oxygenation white both thymoquinone and steroids protect lung tissue from hazardous effects of human gastric juice (pH 1.2) histopathologically. (c) 2005 Elsevier B.V. All rights reserved.