Fluid shear stress (FSS) exerted by blood flow on the endothelium is critical for the maintenance of vascular redox homeostasis. Regions in the vasculature where FSS is low (LS), oscillatory (OS) or turbulent tend to be associated with atherosclerotic lesion development and an impaired redox balance1. High unidirectional, laminar shear stress (HS) maintains endothelial cells (EC) in an “atheroprotective” phenotype by inducing the expression of cytoprotective antioxidant enzymes, such as heme oxygenase-1 (HO-1), which are regulated by the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2)2. LS and OS are associated with an increase in vascular oxidative stress and expression of “pro-inflammatory” genes3. In the current study we have investigated whether FSS alters the expression of Nrf2 and antioxidant defence genes in EC. Bovine aortic endothelial cells (BAEC) were isolated from unwanted aortas obtained from an abattoir and cultured in DMEM containing 10% fetal calf serum. BAEC were seeded into micro channel slides and after 24 h, a fluidic unit air pump system (Ibidi) was used to expose cell monolayers to HS (15 dynes/cm2) or OS (±15 dynes/cm2, 1 Hz) for 2-24 h. Expression of antioxidant proteins Nrf2, HO-1, peroxiredoxin-1 (Prx-1) and glutamate-cysteine ligase catalytic subunit (GCLC) were assessed by western blot analyses and immunofluorescence. Nuclear translocation of Nrf2 elicited by HS was increased after 2h and 24 h compared to static cultures. Western blot analysis revealed that exposure of BAEC to HS caused a significant two-fold increase in Nrf2 protein expression after 24 h vs. static cultures (p<0.05, n=4). HS and OS (24h) significantly increased HO-1 protein levels >17 fold and Prx-1 levels >2.5fold (p<0.05, n=5). Finally HS and OS significantly increased GCLC levels >1.9 fold in comparison to static cultures (p<0.05, n=5). We have demonstrated that HS caused a significant induction of Nrf2 protein expression and an increase in Nrf2 nuclear translocation in BAEC. In addition FSS differentially increased the expression of HO-1, Prx-1 and GCLC. These results suggest that high laminar FSS may protect EC through the enhanced expression of endogenous antioxidant genes.