Clinical intervention for ischemic stroke patients is limited to the acute phase, leaving ~80% of stroke patients without effective pharmacological intervention and unsatisfactory neurological outcome. Therefore, subacute therapeutics that resolve thrombosis and inflammatory processes to support tissue recovery are urgently in need. Plasma kallikrein (PK), a member of the kallikrein-kinin-system, promotes vascular damage, inflammation, and thrombosis. We hypothesize that prolonged PK activation determines stroke severity and impairs tissue recovery. Thus, wild-type mice were subjected to 60 minutes of middle cerebral artery occlusion (tMCAO) followed by direct blocking of PK signalling. On day 3 post-stroke, only mice with similar infarct sizes/neurological deficits received anti-PK or the corresponding IgG-control antibodies. Brain analysis on day 3 and day 7 involved examining thrombosis, blood-brain-barrier disruption, and immune cell infiltration. To evaluate neurological recovery, sensory and motor deficits were assessed. At day 7 after tMCAO, mice showed numerous thrombi in the microcirculation and infiltrated immune cells in the brain in addition to blood-brain-barrier disruption in control mice, which was attributed to tight junction protein degradation and increased permeability. Importantly, treatment with PK antibodies from day 3 onwards significantly stabilized the blood-brain-barrier, decreased microthrombi and led to reduced infarct volume. Vascular stability correlated with abundant angiogenic markers and inflammatory cytokines. PK inhibition in tMCAO mice also resulted in significant accelerated improvement in sensorimotor function, suggesting direct neuroprotection. Hence, pharmacologic inhibition of PK in the subacute phase of ischemic stroke promotes vascular regeneration, and thereby improves functional recovery representing a promising therapeutic option for ischemic stroke treatment.