To observe the effects of Lipoxin A4 （LXA4）in rat models with middle cerebral artery occlusion/reperfusion（MCAO/R) on the number of NLRP3 positive neurons and NLRP3 protein expression in the territory of the ischemic cortex. Methods: Twenty-four adult male Sprague–Dawley rats were randomly divided into sham group, MCAO/R group, and LXA4 group. MCAO/R models were established using an intraluminal filament method. LXA4 group rats were given a 5 μL injection of 0.2 mmol/L LXA4 into the lateral ventricles. The infarct volume, neurological deficit scores, number of NLRP3 positive neurons, and NLRP3 protein expression were observed. Results: LXA4 effectively reduced infarct volume and neurological scores in MCAO/R rats. LXA4 also significantly reduced the number of NLRP3 positive neurons and inhibited the expression of NLRP3. Conclusion: These results suggest that the neuroprotective effects of LXA4 on cerebral ischemia/reperfusion injury are likely achieved by inhibiting the NLRP3 inflammasome signal pathway.