Spinal cord injury (SCI) leads to microvascular damage and the destruction of the blood spinal cord barrier (BSCB), which can progress into secondary injuries, such as apoptosis and necrosis of neurons and glia, culminating in permanent neurological deficits. BSCB restoration is the primary goal of SCI therapy, although very few drugs can repair damaged barrier structure and permeability. Sodium tanshinone IIA sulfonate (STS) is commonly used to treat cardiovascular disease. However, the therapeutic effects of STS on damaged BSCB during the early stage of SCI remain uncertain. Therefore, we exposed spinal cord microvascular endothelial cells to H2O2 and treated them with different doses of STS. In addition to protecting the cells from H2O2-induced apoptosis, STS also reduced cellular permeability. In the in vivo model of SCI, STS reduced BSCB permeability, relieved tissue edema and hemorrhage, suppressed MMP activation and prevented the loss of tight junction and adherens junction proteins. Our findings indicate that STS treatment promotes SCI recovery, and should be investigated further as a drug candidate against traumatic SCI.