【Abstract】 Objective To explore the pathway effect of JAK2/STAT3 in the inflammatory reaction of cerebral ischemia and reperfusion injury. Methods The MCAO SD rat model was prepared by suture-occluded method. 48 rats with MCAO model were randomly divided into model group (24 rats) and AG490 group (24 rats). According the time of perfusion, the groups were divided into 4 groups including 6h, 12h, 24h and 72h subgroups (6 rats in each group). The sham operation group (24 rats) was treated with sham operation. The neurological deficit score was evaluated at 6h, 12h, 24h and 72h after perfusion. The expresses of JAK2, STAT3, IL1β and TNFα in the brain were measured with immunohistochemistry at 6h, 12h, 24h and 72h after perfusion. Results The neurological deficit score and expresses of JAK2, STAT3, IL1β and TNFα in the brain at 6h, 12h, 24h and 72h after perfusion in sham operation group were not different. The neurological deficit score and expresses of JAK2, STAT3, IL1β and TNFα in the brain in model group increased the peak at 24h after perfusion and decreased 72h after perfusion (P＜005). The neurological deficit score and expresses of JAK2, STAT3, IL1β and TNFα in the brain in AG490 group were lower than that of model group (P＜005) and higher than that of sham operation group (P＜005). Conclusion The activation of JAK2/STAT3 signal pathway can promote the inflammatory reaction of cerebral ischemia reperfusion and aggravate the injury by improving the expressions of IL1β and TNFα. AG490 can protect the neurological function by reducing the expressions of JAK2,STAT3,IL1β and TNFα after cerebral ischemia and reperfusion injury.