Objective To explore the effects of H2S on cerebral injury after cardiopulmonary resuscitation (CPR) and its mechanism.Methods Forty-five healthy Sprague-Dawley (SD) rats were randomly (random number) divided into shame-operated group ( group A,n =5 ),resuscitation group ( group B,further divided into four subgroups as per rats sacrificed 6 h,12 h,24 h,and 72 h after resuscitation,n =5),and NaHS pretreatment group ( group C,further divided into 4 subgroups as done in group B).The ratio of water content in brain tissue was calculated.The content of H2S in cerebral cortex of rats in all groups was determined by using universal microplate reader. Immunohistochemistry method was used to count the Nestin-positive cells. Results The content of H2S in hippocampus area of brain showed dramatic changes from rising up at first and then to lowering down to the minimum and finally returning to the original level in 72 h in B group.Compare to group B,brain water content was lesser ( P ＜0.05 or P ＜ 0.01 ) and the levels of Nestin in hippocampus increased in group C(P＜0.05 or P ＜0.01).The neurological deficit score (NDS) was improved (P ＜0.05 or P ＜0.01) and pathological changes in hippocampus of rat brain detected by using hemotoxylin - eosin staining were slighter in group C in comparison with group B.Conclusions Endogenous H2S may involve in the course of formation and progress of cerebral injury after CPR and small dose of NaHS (exogenous H2S) can improve NDS by decreasing cerebral edema and up-regulating Nestin level in hippocampus of brain,playing a protection role in cerebral injury after CPR.