Abstract Body: Stroke is a disease with high mortality worldwide. Malignant stroke, which occurs in the absence of acute phase treatment or insufficient treatment for the recovery of the cerebral parenchyma, has high mortality and is associated with worse functional outcomes. Adequate treatment to prevent the progression of edema and herniation is still a subject that requires further research advancements. The zebrafish (Danio rerio), a vertebrate fish with high genetic and physiological similarity to humans, is used in various research studies related to neuroscience and neurological diseases, such as degenerative and cerebrovascular diseases, including ischemic stroke. Its main characteristics make research more cost-effective and replicable. As the literature mainly presents models that induce global ischemia, mimicking post-hypoxia ischemia, diffuse hypoperfusion or cardiorespiratory arrest, in this study, we propose a new model of focal ischemic stroke, induced by transcranial administration of the potent vasoconstrictor endothelin (ET-1). Animals were distributed into four groups (n=8/each) treated as follows: ET-1, transcranial ET-1, oral vehicle, and transcranial vehicle. A fifth group (n=8) without treatment (naive) was included. Cognitive and locomotor behaviors were analyzed in the Y-maze, 1, 3, 6 and 24 h after treatments. At the end of the tests, the animals were sacrificed and the brains removed for histopathological analysis. Reduced mobility, swimming speed, and distance traveled were observed in the transcranial ET-1 group, but memory was preserved in comparison to the control group (p < 0.05). Brain lesions were confirmed by histopathological analysis, showing neuronal injury and signs of neuroinflammation. It is expected that this model will aid in the advancement of translational research related to the treatment of brain edema and inflammation.