This aim of this study was to investigate the neuroprotective effect of salvianolic acid B (SalB) on intracerebral hemorrhage (ICH) in mice, and to elucidate the underlying mechanism. Methods: A total of 108 C57BL/6J male mice were randomly divided into the Sham, ICH+Vehicle, and ICH+ SalB groups, with 36 mice per group. The ICH model was prepared with type Ⅶ collagenase. Mice in the ICH+SalB group were injected with 30 mg/kg SalB via the tail vein at 2 hours after operation, and mice in the Sham and ICH+Vehicle groups were similarly injected with the same amount of normal saline via the tail vein for 3 consecutive days. On the 3rd day after operation, the modified neurological severity score (mNSS) and corner turn test were conducted to assess behavioral indexes. Further, hematoxylin and eosin (HE) staining was used to observe injury to the brain tissues, brain water content was measured to evaluate cerebral edema, and Evens blue (EB) extravasation test was used to evaluate the permeability of the blood-brain barrier (BBB). In addition, western blot was performed to detect the expression levels of ZO-1 and Occludin to evaluate the integrity of the BBB and to detect the expression levels of MMP-9 and IL-1β as exemplar inflammatory factors. Finally, TUNEL staining was performed to evaluate the number of apoptotic cells, and immunofluorescence staining using Iba1 and MPO was adopted to evaluate microglia activation and neutrophil exudation. Results: The results of mNSS testing showed that the neurologic deficit degree in the ICH+SalB group was lower than that in the ICH+Vehicle group (P<0.05), while in the corner turn test, the number of right turns in the ICH+SalB group was less than that in ICH+Vehicle group (P<0.05). HE staining showed that the degree of brain tissue injury and hematoma area in the ICH+SalB group were reduced compared to the ICH+Vehicle group (P<0.05). Brain water content analysis showed that the degree of cerebral edema in the ICH+SalB group was less than that in the ICH+Vehicle group (P<0.05), and the EB extravasation level in the ICH+SalB group was lower than that in ICH+Vehicle group (P< 0.05). Further, the western blot results showed that the expression levels of MMP-9 and IL-1β in ICH+SalB group were lower than those in the ICH+Vehicle group (P<0.05), while the expression levels of ZO-1 and Occludin in ICH+SalB group were higher than those in the ICH+Vehicle group (P<0.05). TUNEL staining showed that the number of apoptotic cells in the ICH+SalB group was lower than that in ICH+Vehicle group (P<0.05). Finally, the immunofluorescence staining results showed that the Iba1 and MPO levels were lower in the ICH+SalB group than in the ICH+Vehicle group (P<0.05). Conclusion: Overall, our results indicate that SalB may improve neurological function and play a neuroprotective role by reducing cerebral edema, the level of inflammatory factors, and stabilizing the blood-brain barrier in mice with ICH.