Objective: To investigate the efficacy of citicoline combined with alteplase in the treatment of acute cerebral infarction (ACI) and its effect on cerebral blood flow velocity and inflammatory factors. Methods: Sixty patients with ACI were divided into control group and experimental group by random number table method, with 30 cases in each group. Both groups were given conventional treatment such as anti-platelet aggregation and anticoagulation. In addition, the control group was treated with alteplase thrombolytic therapy, and the observation group was treated with citicoline combined with alteplase. Both groups were treated for 14 days. The neurological function (National Institutes of Health Stroke Scale (NIHSS)), daily living ability (Barthel Index (BI)), cerebral blood flow velocity and serum inflammatory factors (C-reactive protein (CRP), tumor necrosis factor-α (TNF-α)) of the two groups before and after treatment were statistically analyzed, and the efficacy and adverse reactions of the two groups were compared. Results: Compared with the control group (73.33%), the total effective rate of the observation group (96.67%) was higher (P<0.05). After treatment, compared with the control group, the NIHSS score of the observation group was lower(P<0.05), and the BI score was higher (P< 0.05). After treatment, the cerebral blood flow velocity in the observation group was increased(P<0.05), and the levels of serum CRP and TNF-α were decreased (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Citicoline combined with alteplase is effective in the treatment of ACI, which can better reduce the neurological deficit of patients. The mechanism may be related to the improvement of cerebral blood flow velocity and the reduction of inflammation level.