Objective To observe the effect of astragaloside IV on inflammatory factors and ultrastructure in rats with cerebral ischemia reperfusion. Methods A cerebral ischemia reperfusion injury model was established in Sprague- Dawley (SD) rats by middle cerebral artery occlusion. Forty male SD rats were randomly divided into a sham operation group, model group (cerebral ischemia reperfusion injury group), astragaloside IV group and nimodipine group ( positive drug group). All groups except the sham operation group were reperfused for 24 hours after 2 hours of cerebral ischemia. In the treatment groups, astragaloside IV and nimodipine were respectively injected intraperitoneally one week before model establishment. The Zea Longa scoring method was used to detect neurological deficits of rats in each group. TTC staining was used to detect the volume of cerebral infarction. The ELISA method was used to detect the inflammatory factor levels in brain tissue, including tumor necrosis factoR-α ( TNF-α), interleukin - 6 ( IL-6) and interleukin - 1β ( IL-1β). Nissl staining was used to observe neuronal damage in the cerebral cortex. Transmission electron microscopy was used to observe the ultrastructural changes of neurons in the cerebral cortex. Results In the sham operation group, no neurological deficits or cerebral infarction was observed, and abundant nerve cells and Nissl bodies were present. The cells were arranged neatly, and the ultrastructure was clear and normal. Compared with the sham operation group, neurological impairment was more serious in the model group. The cerebral infarction volume was significantly increased (P<0. 05). The inflammatory factor content (TNF-α, IL-6 and IL-1β) was increased (P<0. 05). The cells had a disorderly arrangement, the nuclei were deformed and showed pyknosis, and the chromatin was unevenly distributed. Compared with the model group, the neurological function of rats in astragaloside IV and nimodipine groups was improved, the cerebral infarction volume was decreased (P<0. 05), the TNF-α, IL-6 and IL-1β content was significantly decreased (P<0. 05), the cell arrangement was more orderly, the cell nucleus was regular, and the chromatin distribution was more uniform. Conclusions Astragaloside IV can inhibit cerebral ischemia reperfusion injury and improve the ultrastructural changes of nerve cells in rats. Its mechanism may be related to alleviation of the inflammatory reaction.