Acute lung injury (ALI) is a major cause of morbidity and mortality in humans and animals. In traditional and modern medicines, Nigella sativa extract, thymoquinone (TQ) has several benefits. Here, we examined the counter effects of TQ in ALI induced by Lipopolysaccharide (LPS). Tissue sections and serum samples were collected from the following groups of rats: i) none treated control, ii) TQ only, iii) intratracheally (I.T) installed with LPS 200 µg/rat once, iv) TQ protected received intraperitoneally (I.P) 1 mg/rat for one week. Samples were subjected to histopathology, immunohistochemistry, ELISA and electron microscopy. TQ-treated rats revealed reduction in peribronchial, perivascular and interstitial inflammatory edema, thickening of interalveolar septa, inflammatory exudates in the lumens of airways and alveoli, hypertrophied smooth muscles of pulmonary blood vessels and airways and hyperplasia of bronchial associated lymphoid tissue (BALT). Electron microscopy revealed highly activated pneumocyte with vacuolated cytoplasm in TQ-treated group. Immunomodulators, IL1ᵦ and TNFα showed lower levels in TQ-treated group. Meanwhile, NF-κB was absent according to immunohistochemistry. It could be concluded that TQ restores lung architecture and reduces inflammatory Immunomodulators in ALI.