Inflammation after stroke consists of activation of microglia/astrocytes in situ and infiltration of blood-borne leukocytes, resulting in brain damage and neurological deficits. Mounting data demonstrated that most natural components from medicinal plants had anti-inflammatory effects after ischemic stroke through inhibiting activation of resident microglia/astrocytes within ischemic area. However, it is speculated that this classical activity cannot account for the anti-inflammatory function of these natural components in the cerebral parenchyma, where they are detected at very low concentrations due to their poor membrane permeability and slight leakage of BBB. Could these drugs exert anti-inflammatory effects peripherally without being delivered across the BBB? Factually, ameliorating blood-borne neutrophil recruitment in peripheral circulatory system has been proved to reduce ischemic damage and improve outcomes. Thus, it is concluded that if drugs could achieve effective concentrations in the cerebral parenchyma, they can function via crippling resident microglia/astrocytes activation and inhibiting neutrophil infiltration, whereas the latter will be dominating when these drugs localize in the brain at a low concentration. In this review, the availability of some natural components crossing the BBB in stroke will be discussed, and how these drugs lead to improvements in stroke through inhibition of neutrophil rolling, adhesion, and transmigration will be illustrated.