Sufficient understanding of the systemic inflammatory response after stroke will make the therapeutic strategy targeting inflammation more feasible. Here, we aimed to identify the globally alterations of circulating cytokines in super-acute ischemic stroke (AIS).A broad panel of 65 cytokines was measured in the plasma of twenty-eight AIS patients within 6 h after stroke onset (n = 28), cerebral hemorrhagic patients (n = 28) and healthy controls (n = 18). The diagnostic power of the candidate cytokines and their relationship with the number of lymphocytes and neutrophils were analyzed by receiver operating characteristic (ROC) and spearman rank correlation respectively.The expression level of plasma IL-1beta, IL-2, IL-2R, IL-5, IL-10, CD40L, HGF, MIP-3alpha and MMP-1 were obviously up-regulated, while IL-16 was down-regulated in AIS patients compared to healthy controls. Among them, IL-2R, IL-10, IL-16, MIP-3alpha, and MMP-1 were specially altered in AIS patients, while IL-1beta, IL-2, IL-5, CD40L and HGF were elevated simultaneously in AIS and hemorrhagic stroke patients. Interestingly, IL-6 and TNF-beta were found to be key facytors among the 65 cytokines to distinguish hemorrhage from ischemia. Furthermore, IL-1beta, IL-16, CD40L and HGF were obviously correlated with the number of lymphocytes, and IL-1beta and IL-16 were significantly associated with the number of neutrophils in AIS patients. These results suggest that lymphocytes and neutrophils associated inflammation may play a pivotal role in AIS.Importantly, except for some mutual pathological processes, AIS and hemorrhage had their own distinctive pathogenesis, and transformation of this knowledge to further research may provide novel treatment strategy for AIS.Copyright © 2022 Elsevier Ltd. All rights reserved.