Objective To investigate the effects of tirofiban on neuron injury in acute cerebral infarction (ACI) rats through silent information regulator factor 2-related enzyme 1 (SIRT1)/vascular endothelial growth factor (VEGF) signaling pathway. Methods Seventy-five SD rats were randomly divided into sham group, model group, tirofiban (60 μg/kg) group, SIRT1 inhibitor (5 mg/kg SIRT1 specific inhibitor EX-527) group, and tirofiban＋SIRT1 inhibitor group, with 15 rats in each group. Except for the sham group, ACI models were constructed in the other 4 groups. The rats in each group were scored for neurological function. Triphenyl tetrazolium chloride staining was used to analyze the cerebral infarction volume percentage of rats. The serum malondialdehyde level was measured by thiobarbituric acid method, glutathione peroxidase (GSH-Px) level was detected by colorimetry, and superoxide dismutase (SOD) level was detected by microplate test. Hematoxylin-eosin staining was used to detect the pathological changes of rat brain tissue. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to detect the apoptosis of rat neurons. Western blotting was used to detect the expression of SIRT1 and VEGF proteins in the hippocampal tissue of rats. Results Compared with the sham group, the pathological damage of the hippocampus was more serious in the model group, the neurological function score, cerebral infarction volume percentage, serum malondialdehyde level and neuronal cell apoptosis rate were significantly increased (all P＜0.05), and the levels of serum GSH-Px and SOD and the expression levels of SIRT1 and VEGF proteins in the hippocampal tissue were significantly decreased (all P＜0.05). Compared with the model group, the pathological damage of the hippocampus was decreased in the tirofiban group and tirofiban＋SIRT1 inhibitor group, the neurological function scores, cerebral infarction volume percentage, serum malondialdehyde levels and neuronal cell apoptosis rates were significantly decreased (all P＜0.05), and the levels of serum GSH-Px and SOD and the expression levels of SIRT1 and VEGF proteins in the hippocampal tissue were significantly increased (all P＜0.05); however, the corresponding indexes of the rats in the SIRT1 inhibitor group showed an opposite trend (all P＜0.05). Conclusion Tirofiban may inhibit oxidative stress and neuron apoptosis by activating SIRT1/VEGF signaling pathway, thus alleviating neuron injury in ACI rats.