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Vitex agnus‐castus (VAC, Verbenaceae) is widely used in Chinese traditional medicine as an antiinflammatory agent. This study aimed to explore the efficacy of the VAC extract to protect against lipopolysaccharide (LPS)‐induced acute lung injury. The results have shown that VAC had a potent protective activity against LPS‐induced acute lung damage. It significantly decreased pulmonary edema as there was a significant decrease in lung wet/dry ratio and in protein content. VAC also decreased the lactate dehydrogenase's activity in the bronchoalveolar fluid. VAC ameliorated LPS‐induced inflammatory cells infiltration into the lung tissue and reversed the histopathological lesions of the lung. Furthermore, VAC counteracted LPS‐induced oxidative stress as it attenuated the lipid peroxidation marker, malondialdehyde, in the lung. VAC increased the antioxidant activity as evident by elevated superoxide dismutase activity and increased reduced glutathione content in the lung tissue. Collectively, VAC has a protective activity against LPS‐induced acute lung damage through its antioxidant potential. Practical applications Vitex agnus‐castus has been used in various traditional medicines for treating various ailments as digestive complains, acne, rheumatic pains, menstrual irregularities, premenstrual syndrome, infertility, and hyperprolactinemia. Its leaves are used as a spice and the fruits are used as a substitute for pepper. VAC food supplements are used by women against psychic and somatic premenstrual symptoms. The findings of this study can demonstrate the potent protective activity of the VAC extract against LPS‐induced acute lung damage due to its antioxidative effects. Therefore, VAC could be developed as a health functional food to improve acute lung damage and many diseases caused by oxidative damage.

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