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Recombinant tissue plasminogen activator (r-tPA) is the first-line drug for the treatment of acute ischemic stroke, despite it may lead to a variety of complications in some cases. In patients with extensive stroke, infarction of the brain can cause suppression of the respiratory center in the brain leading to neurogenic pulmonary edema that potentially causes respiratory failure. Its etiology is either due to a neurogenic or non-neurogenic process. Nevertheless, the definite pathophysiology of these circumstances remains unclear. In this study, we reported four cases of post-thrombolytic ischemic stroke patients who suffer from pulmonary edema with different symptoms and onset times as well as we discuss the possible explanation behind these different outcomes.