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The neuroprotective effect of Zhutan Tongluo Tang is associated with the activities of the fibrinolytic system. Thus the present study was designed to investigate therapeutic effects of Zhutan Tongluo Tang on intracerebral hemorrhage in rats, induced by injecting collagenase into one side of the caudate nucleus. Fibrinolytic indices including tissue plasminogen activator, plasminogen activator inhibitor-1 and D-Dimer were determined. The results obtained demonstrated that Zhutan Tongluo Tang treatment could alleviate the neural and behavioral impairments of intracerebral hemorrhaging rats. Increased frequencies of placing their forelimb correctly and decreased frequencies of turning left were observed. Enzyme linked immunosorbent assay showed that Zhutan Tongluo Tang could significantly elevate the concentration of plasma tissue plasminogen activator and D-Dimer, while depress plasminogen activator inhibitor-1. Immunohistochemistry demonstrated increased levels of catalase and glutathione in whole brain rat tissue following intracerebral hemorrhage. In addition, elevated expression of Bcl-2 in various hippocampal regions was seen. These findings describe the ability of Zhutan Tongluo Tang to activate the fibrinolytic system, and suggests that antioxidant and apoptosis inhibitory mechanisms may be playing a crucial role in protecting against collagenase-induced intracerebral hemorrhage.