The dietary-derived isothiocyanate sulforaphane (SFN) is an electrophilic inducer of the redox-defence transcription factor Nrf2, acting on the Cys-151 residue of its cytosolic sequestration partner, Keap1. In addition, sulforaphane exhibits anti-inflammatory effects through inhibition of NFκB, and at higher concentrations affects cytoskeletal polymerization. SFN pre-treatment has been shown to reduce acute plasma protein leakage into the brain parenchyma in rodent models of focal ischemia-reperfusion, implying moderation of vascular permeability. While inflammatory mediators associated with ischemia-reperfusion are known to increase vascular permeability via redox pathways in the rat (bradykinin via COX/LOX and IL1β via NOX2) the precise mechanism of vascular protection by SFN is undefined. The ileal artery of a freshly killed Sprague-Dawley rat was cannulated orthogradely and branches that did not lead to the cremaster muscle were ligated. The cremaster microcirculation was flushed with a high Mg2+ & K+ solution containing heparin. The muscle was spread over a transparent support and superfused with Krebs buffer at 37oC and perfused with a buffer containing albumin (5 mg.ml-1) and FITC-albumin (5 mg.ml-1). Permeability was obtained from the rate of change in fluorescent signal across the wall of a selected venule (k) and its diameter (d): P = kd/4 when perfusion was stopped. Bk (0.1µM in the presence of 10µM each of captopril and thiorphan) was applied in the superfusate for 1 min, and IL-1β (30pM) was applied topically for 10 min before being washed off. The effects of sulforaphane were assessed by both acute superfusion (1nM to 100µM) and sulforaphane pre-treatment 5mg.kg-1 i.p. 24h before surgery. The permeability response to bradykinin (0.20 ± 0.08 10-6 cm s-1; mean ± sem, n =5;) was unaffected by SFN pre-treatment (0.20 ± 0.19). IL1β pretreatment resulted in an increased response to Bk (1.64 ± 0.55). Both responses were abolished by scavenging with and superoxide dismutase and catalase (0.1 ± 0.2; S&C 100U/ml each). SFN pre-treatment had no affect on the response to Bk, but abolished the IL1β potentiated Bk response (0.13 ± 0.06). Acute SFN application had little effect on permeability at doses below 0.1µM, but SFN 1µM and 10µM resulted in a significant permeability response (0.60 ± 0.05 and 0.60 ± 0.15). Intriguingly higher SFN doses resulted in much lower permeability increases, and these high doses blocked the permeability response to Bk. This novel finding of a direct permeability response to SFN, in combination with an ability to acutely block the Bk permeability response, implies additional Nrf2-independent effects may underlie physiological cerebrovascular protection.