Sepsis is a systemic inflammatory response syndrome (SIRS) that occurs when the body's immunity overreacts to an infection. It is followed by life-threatening medical consequences, including multiple organ failure (MOD). Dexmedetomidine (DEX) is a selective 2 adrenergic agonist that is used as a short-term sedative in the ICU. Apart from improving sepsis prognosis, it is believed to have an organ protecting function. Our study aimed at confirming DEX ameliorative role in sepsis-induced organ damage. We also studied DEX mitigating effect on sepsis-induced acute lung injury (ALI) and elucidated the possible mechanism. Thirty rats were randomly assigned into three groups (n=10): sham, cecal ligation and puncture (CLP)-induced sepsis, or DEX-treated CLP (DEX + CLP). 15 minutes before the CLP procedure, a prophylactic dosage of DEX (5g/kg) was given intraperitoneally (IP). Animals were slaughtered 48 hours after the surgery was completed. Histological examination for tissue samples from lung, liver and kidney. CD54 expression in lung tissue was also investigated. Blood was also taken for hematological analysis. CLP rats showed different pathological lesions in lung, kidney and liver. We reported severe pulmonary tissue damage in CLP group accompanied with enhanced CD54 expression. DEX decreased the severity of histopathological changes in the affected organs and reduced the expression of CD54 in the lung tissue as well. However, DEX could not improve sepsis-induced hematological impairment. DEX attenuated sepsis through decreased CD54 expression in the lung as well as its hepato-renal protective effect in the CLP model.