Introduction: Sepsis is a life-threatening excessive systemic inflammatory reaction syndrome to infection that usually occurs in patients with bacteremia. The respiratory system is one of the structures most affected by acute organ damage. Melatonin plays an important role in re gulating various physiological functions of the body, including antioxidant and anti- inflammatory. Ramelteon (RAME) is the first melatonin receptor agonist confirmed for clinical use. The goal of this study is to determine the effects of RAME on endotoxin- induced septic lung injury in rats. Materials and Methods: Thirty-two female rats were separated randomly into four groups (n =8). Group healthy received intraperitoneal normal saline, group sepsis received intraperitoneally 10 mg/kg lipopolysaccharide (LPS), group sepsis+RAME2 received 10 mg/kg LPS plus 2mg/kg RAME, and group sepsis+RAME4 received 10 mg/kg LPS plus 4mg/kg RAME. RAME was administered by oral gavage 1 hour before LPS administration. The lung tissues were collected 12 hours after LPS administration and in vestigated molecularly (qRT- PCR analyses of Tumor Necrosis Factor-α, nuclear factor kappa-β, and interleukin 1-beta mRNA expression) and histopathologically (s taining with Harris Hematoxylin and Eosin Y). Results: TNF-α, NF- κβ, and IL-1β levels significantly decreased dose-dependent in the septic rats following RAME administration. RAME admi nistration ameliorated histopathological injury in lung tissues due to sepsis. Conclusion: RAME ameliorated the inflammatory response in endotoxin-induced sepsis. These findings suggest that RAME can be a promising agent by contributing to alternative preventive treatment methods for sepsis with its anti- inflammatory effect.