Objective To study the immunomodulation effects of different dosage of dexmedetomidine (Dex)in the septic shock model of rats after cecal ligation and puncture (CLP).Methods After CLP, 48 wistar rats were randomly (random number)allocated in four groups:(1)CLP group;(2)small-dose Dex group [2.5 μg/(kg·h)];(3)medium-dose Dex group [5.0 μg/(kg·h)];(4) large-dose Dex group [10.0 μg/(kg·h)].HLA-DR (human leukocyte antigen-DR)and plasma cytokine (IL-4, IL-6,IL-10 and TNF-α)were measured,meanwhile mean arterial blood pressure (MAP),heart rate (HR)and mortality were also documented at 1,3,and 5 h after the CLP procedure.Results There were no obvious differences in HLA -DR level,levels of inflammatory mediators,MAP and HR among there Dex treatment groups.Compared with CLP group,HLA-DR level decreased in three Dex treatment groups (P =0.020)and pro-inflammatory mediator (IL-6)increased at 3 h (P =0.011 )then declined at 5 h with decreased HR (P <0.01),and without obvious change in MAP (P =0.124),and all of them led to a significantly decrease in the mortality.The mortalities in CLP group,small dose group,medium dose group and large dose group were 91.7%, 66.7%, 25.0% and 18.0%, respectively. Conclusions Dexmedetomidine used in rats with septic shock rats partially induced immunomodulation initiated within 5 h after CLP evidenced by decreased HR,maintenance of MAP and reduction of mortality rate in dose-dependent fashion.