Astrocytes are closely associated with cerebrovascular endothelium, providing functional and metabolic support. The relationship between these two cell-types has been defined as gliovascular complex. Activation of the redox sensitive transcription factor Nrf2 in the brain is a key mechanism underlying endogenous protection against oxidative stress. In the present study, we have investigated expression of Nrf2, constitutive antioxidant enzyme heme-oxygenase-2 (HO-2) and Nrf2-inducible HO-1 in cerebral microvessels after experimental stroke. Male Sprague-Dawley rats (250-300g) were subjected to 70 min right middle cerebral artery occlusion (MCAo) under isoflurane anaesthesia and followed by 4, 24 or 72 h reperfusion. HO-2, HO-1 and Nrf2 were detected by immunofluorescence and immunohistochemistry in brain coronal sections along with brain injury and cell markers. Cerebral ischaemia-reperfusion did not change constitutive HO-2 expression, however levels were significantly higher in perivascular astrocytes than endothelial cells. HO-1 expression was induced in microvessels of the peri-infarct region after 4-72 h, where it was mainly expressed by perivascular astrocytes. Nrf2 expression was significantly increased in microvessels after stroke between 4-24 h, peaking after 4h and remaining elevated after 72 h in perivascular astrocytes. In the endothelium, Nrf2 peaked after 24 h and declined by 72 h. In conclusion, astrocytes play a central role in protecting the gliovascular complex by expressing antioxidant enzymes. As Nrf2 and HO-1 expression are increased in cerebral microvessels following stroke, the Nrf2 defence pathway may be a therapeutic target to protect the brain against stroke.