Diabetes mellitus is an independent risk factor for ischemic stroke.Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes.Stellate ganglion block can effectively regulate the inflammatory response.Therefore,it is hypothesized that stellate ganglion block could be a potential therapy for ischemic stroke in diabetic subjects.In this study,we induced diabetes mellitus in rats by feeding them a high-fat diet for 4 successive weeks.The left middle cerebral artery was occluded to establish models of ischemic stroke in diabetic rats.Subsequently,we performed left stellate ganglion block with 1％ lidocaine using the percutaneous posterior approach 15 minutes before reperfusion and again 20 and 44 hours after reperfusion.Our results showed that stellate ganglion block did not decrease the blood glucose level in diabetic rats with diabetes mellitus but did reduce the cerebral infarct volume and the cerebral water content.It also improved the recovery of neurological function,increased 28-day survival rate,inhibited Toll like receptor 4/nuclear factor kappa B signaling pathway and reduced inflammatory response in the plasma of rats.However,injection of Toll like receptor 4 agonist lipopolysaccharide 5 minutes before stellate ganglion block inhibited the effect of stellate ganglion block,whereas injection of Toll like receptor 4 inhibitor TAK242 had no such effect.We also found that stellate ganglion block performed at night had no positive effect on diabetic ischemic stroke.These findings suggest that stellate ganglion block is a potential therapy for diabetic ischemic stroke and that it may be mediated through the Toll like receptor 4/nuclear factor kappa B signaling pathway.We also found that the therapeutic effect of stellate ganglion block is affected by circadian rhythm.