Obesity is a major cause of morbidity and mortality and is a risk factor for many diseases such as cardiovascular disorders, type II diabetes and stroke. Some of these obesity-related complications (e.g. type II diabetes) have been linked to changes in inflammation, as obesity is characterised by chronic low-grade inflammation (1). Obesity is also associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity, such as leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice display altered centrally-mediated sickness behaviour in response to acute systemic infections (2-4). Although obese ob/ob and db/db mice are useful models of obesity, genetic mutations leading to leptin or leptin receptor deficiency have been only identified in a small subset of the obese population in humans, and to date diet-induced obese (DIO) rodents remain the most relevant model for human obesity. We have shown recently that DIO mice display a heightened and prolonged response to infection caused by lipopolysaccharide (LPS), and these observations maybe due to changes in the inflammatory response. Growing evidence suggests that inflammation modulates the response to acute brain injury (5). Peripheral inflammatory stimuli, such as infection, increase the risk of stroke and are associated with poorer outcome (6,7). As obesity is a risk factor for stroke, and is associated with changes in the inflammatory response, we determined the effects of obesity on the outcome of stroke, and if changes in inflammation maybe involved. Ischaemic damage was exacerbated in obese ob/ob mice compared to lean controls 24h after experimental stroke and this effect was independent of leptin. This enhancement in damage was accompanied by an increased susceptibility of haemorrhagic transformation in ob/ob mice. We also observed changes in the number of inflammatory cells in the obese mice. These data demonstrate that obesity is detrimental to the outcome of stroke, and is associated with an increased risk of haemorrhagic transformation. Furthermore, the altered inflammatory state associated with obesity maybe involved in the detrimental affect this condition has on neuronal injury.