Ischemic stroke is a kind of stroke in which the blood supply to the brain is disrupted, resulting in serious neurological deficits. Among stroke patients, about 87% of the cases are ischemic stroke. Neuroinflammation is one of the main pathological conditions of stroke injury. CKLF1 is a non-classical CC-type chemokine discovered in 2001, which showed strong chemotactic activity on monocytes, neutrophils, and lymphocytes. CKLF1 is most abundant in the fetal brain, but absent in the healthy adult. Growing evidence shows that CKLF1 is reactivated and expressed in adult stroke animal models and participates in multiple processing of neuroinflammatory responses. CKLF1 could activate the polarization of microglia to produce inflammatory mediators and trigger inflammation in the injured brain. And then they drove peripheral immune cells such as neutrophils to recruit into the injured brain. These stimulated the greater immune responses and destroyed the fragile blood-brain barrier (BBB). We believe that CKLF1 plays an important role in the course of ischemic stroke. However, the development of its biological activity and drug discovery lacks systematic literature reports. Thus, we collected the published data and made this review, to briefly describe the role of CKLF1 in ischemic stroke, and explained its mechanism of aggravating ischemic stroke. Moreover, some potential anti-stroke drugs have been discovered, indicating that CKLF1 is a potential target for the treatment of ischemic stroke.