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Objective: To investigate the relationship between leukoaraiosis (LA)and hemorrhagic transformation(HT)and neurological outcome at 3 months after recombinant tissue plasminogen activator(rt-PA) treatment in patients with acute ischemic stroke.Methods: Prospective clinical,1aboratory, and radiological data from patients with acute ischemic stroke who had received intravenous rt-PA therapy in our hospital were retrospectively reviewed. The severity ratings of LA were evaluated by Age-related white matter changes scale (ARWMC) scale. In order to detect hemorrhagic transformation, all the patients in thrombolysis group had the second head CT scan at 24 h after thrombolysis. sICH was assessed according to the European Collaborative Acute Stroke Study II (ECASS II) criteria. Hemorrhagic transformation after thrombolytic therapy and clinical neurological outcome based on modified Rankin scale(mRS)at 3 months were also analyzed. Favorable outcome as mRS 0-1 and unfavorable outcome as mRS 2-6 were defined.Results: 584 patients receiving intravenous rt-PA treatment in this study were finally enrolled. The mean age was (63.1 ± 9.7) years and 250 cases (42.9%) in women. Door to needle time was (170.4 ± 44.4) min, pretreatment National Institutes of Health Stroke Scale score was 13.76 ± 6.18. Hemorrhagic transformation was found in 83 cases (14.2%). Logistic regression analysis showed that the severity of LA was associated with hemorrhagic transformation, the odds ratios ranged from 2.017(95% CI 1.419 ~ 2.915) to 2.541 (95% CI 1.714 ~ 3.368). Dicho-Logistic regression analysis showed that WMHs Score was the independent risk factor of unfavorable neurological outcome (OR = 1.735, 95% CI 1.236 ~ 2.442).Conclusion: The severity of LA is associated with an increased risk of sICH and poor functional outcome after IV or intra-arterial thrombolysis for acute ischemic stroke.