Objective To investigate the regulatory effect of schisandrin(Sch) B on pathological injury, inflammatory response, and nuclear factor-kappa B (NF-κB) expression in lung tissue of rats with sepsis and acute lung injury induced by lipopolysaccharide (LPS). Methods A rat model of acute lung injury was established by intratracheal instillation of 40 mg/kg LPS, and intervention treatment was performed by intraperitoneal injection of 80 mg/kg Sch B at 1 hour before surgery. The lung wet/dry mass ratio was measured; BCA kit was used to measure total protein in bronchoalveolar lavage fluid (BALF), and the abalone counter was used to calculate the number of white blood cells; HE staining was used to observe lung injury. ELISA was used to measure the content of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in lung tissue; related kits were used to measure the content of malondialdehyde (MDA) and superoxide dismutase (SOD) in lung tissue; Western blot was used to measure the expression levels of nuclear factor-kappa B p65 (NF-κB p65), pIκBα, and Toll-like receptor 4 (TLR4) in lung tissue. Results Compared with the model group, the schisandrin B group had significant reductions in lung wet/dry mass ratio, total protein and number of white blood cells in BALF, pathological injury, and the content of TNF-α, IL-1β, and IL-6 (P<0.05), as well as a significant reduction in MDA content, a significant increase in SOD content, and significant reductions in the expression of NF-κB p65, pIκBα, and TLR4 (P<0.05). Conclusion In rats with sepsis and acute lung injury induced by LPS, schisandrin B can alleviate pathological injury of lung tissue and inhibit inflammatory response, oxidative stress response, and activation of the NF-κB pathway.