We suppose that apigenin may inhibit the cellular process of sepsis‐induced lung injury, which is considered to be a major cause of morbidity and mortality, and may improve inflammation and oxidative stress. The aim of this study was to investigate the potential protective effect of apigenin in a rat model of polymicrobial sepsis. Eight groups consisting of a total of 64 female Wistar albino rats were used for this study. Pro‐inflammatory (TNF‐α, IL‐1‐β, IL‐6) and anti‐inflammatory (TGF‐β, IL‐10) cytokine levels were measured with the enzyme‐linked immunosorbent assay technique, oxidant/antioxidants parameters were measured using the spectrophotometric method and Bax and Caspase‐3 immunohistochemical methods. TNF‐α, TGF‐β, IL‐1β, and IL‐6 levels significantly increased in the sepsis‐induced group than in the control groups, while IL‐10 levels decreased. Lipid peroxidase (LPO), an oxidative stress marker, increased, while the antioxidant defense parameters of superoxide dismutase (SOD), catalase (CAT) activities, glutathione (GSH) levels decreased. Although Bax and Caspase‐3 immunoreactivity and H score levels significantly increased in the sepsis group, significant decreases were found in the groups treated with apigenin. In conclusion, we are of the opinion that apigenin treatment improves lung injury by inhibiting oxidative stress and inflammatory cell damage.