Chrysin (CR) is a flavone found in propolis and many plants. Lipopolysaccharide (LPS) is a component of the cell wall of gram-negative bacteria that causes sepsis. The purpose of this study was to investigate the effects of CR on LPS-induced sepsis in rats. LPS intraperitoneal and a single dose and CR were given orally for 10 days. Rats were sacrificed, blood samples were taken, liver, lung, and kidney tissues were dissected, homogenized, and histopathological analysis was carried out. When CR groups compared to sepsis group, CR significantly decreased the serum levels of aspartate transaminase (AST) and alanine aminotransferase (ALT), interleukin-1 beta (IL-1 beta), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and levels of malondialdehyde (MDA) in tissues. CR also increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in tissues. Histopathological findings were consistent with biochemical findings. Conclusion, CR could reduce the oxidative stress markers and cytokines in sepsis. Practical applications Our approach is to determine the antioxidant and anti-inflammatory effects of chrysin, known as a flavolonoid, which are found in many plants and foods such as honey and propolis. In this study, experimental sepsis model was created using LPS. According to the results of the study, CR can attribute to the ameliorating of oxidative damage in tissues (lung, liver, and kidney) and it can suppress the sepsis-associated acute tissue injury via reduction of inflammation in rats. Even, CR can be used as a pharmacological agent in inflammatory diseases caused by other sources and in many cases causing oxidation.