Superior sagittal sinus thrombosis (SSST) is a form of cerebral venous sinus thrombosis (CVST) routinely treated with anticoagulation therapy. Anticoagulation and thrombolysis treatment effects on neurological function, venous recanalization and brain edema were compared after SSST in rats. Male Sprague-Dawley rats underwent non-fatal SSST induction and were divided into no treatment (control), anticoagulation (heparin), carotid artery thrombolysis and local thrombolysis groups (each n = 50). Within each group, an equal number of rats (n = 10) were treated with anticoagulation and thrombolysis at day 3 or weeks 1, 2, 3 or 4 following SSST. Magnetic resonance venography (MRV) was conducted within 24 h of anticoagulation and thrombolysis treatments to determine recanalization, structural abnormalities and cerebral edema quantitated by wet-dry methods. Neurological function (Rotarod test) and histological abnormalities were compared. Severe brain edema, flattened gyri and coronal swelling were observed following SSST. Recanalization rates in carotid artery and local thrombolysis were higher than in anticoagulation (both p < 0.001). Carotid artery and local thrombolysis brain water contents were 79.6 +/- 0.1% and 79.2 +/- 0.1%, respectively, significantly lower than 83.9 +/- 0.1% and 84 +/- 0.1% in anticoagulation and controls, respectively (all p < 0.05), after treatments at day 3 following SSST. Increasing SSST onset to treatment time worsened neurological function (p < 0.05). Maximum treatment benefits were observed <2 weeks post-SSST using local thrombolysis and, to a lesser extent, carotid artery thrombolysis. Thrombolysis may produce better functional outcomes if employed early rather than as a second-line treatment following anticoagulant failure.