Abstract： Objective:To explore the efficacy of hyperbaric oxygen assisting clopidogrel, an antiplatelet drug, in the treatment of acute cerebral infarction (ACI) and its effect on platelet activation.Methods:A total of 144 ACI patients admitted to the Department of Neurology of Qingyang People’s Hospital from January 2017 to December 2018 were selected and randomly divided into control group and observation group with 72 cases in each group. The control group was treated with clopidogrel on the basis of conventional treatment, and the observation group was additionally treated with hyperbaric oxygen therapy on the basis of the treatment of the control group. The clinical efficacies of the two groups were compared. The scorings of Montreal cognitive assessment Scale (MoCA), mini-mental state examination (MMSE), and Barthel index were performed before and after treatment. Serum platelet activating factor (PAF) and platelet α-granule membrane glycoprotein (CD62P) were measured.Results:In the observation group, 33 patients were cured, 24 showed markedly effects, and 10 showed some improvements. The total effective rate (93.06%) in the observation group was significantly higher than that (84.72%) in the control group with a statistically significant difference ( P<0.05). After treatment, the scores of MoCA, MMSE, and Barthel index in the observation group were 25.83±1.73, 25.46±2.33, and 76.25±4.78, respectively, which were significantly higher than those in the control group (23.77±1.94, 21.85±2.48, and 65.36±5.12) ( P<0.05). In the two groups, the serum levels of PAF and CD62P after treatment were significantly lower than those before treatment, and the differences were statistically significant ( P<0.05), moreover, the reduction of serum levels of PAF and CD62P in the observation group were better than those in the control group, with statistically significant differences ( P<0.05). Conclusion:Hyperbaric oxygen assisting clopidogrel in the treatment of ACI can effectively reduce serum levels of PAF and CD62P, and reduce platelet activation to prevent thrombosis, thus the combined therapy can significantly improve the therapeutic effect of ACI and effectively restore the cognitive and physiological functions of patients, which is worthy of clinical promotion and application.