Obesity is an independent risk factor for stroke and is associated with poorer outcome after stroke. We investigated whether this poorer outcome is related to brain microvascular disruption. Focal cerebral ischaemia was induced in lean or obese (ob/ob) mice by transient middle cerebral artery occlusion. The incidence of haemorrhagic transformation and the volume of ischaemic brain damage were significantly greater in obese mice. Blood-brain barrier permeability and brain microvascular MMP-9 expression were also markedly increased in obese mice. These effects were independent of leptin or glycaemic status, suggesting that obesity potentiates brain microvascular disruption after experimental stroke.