The study aimed to investigate the efficacy of edaravone combined with recombinant tissue plasminogen activator (rt-PA) in treatment of acute cerebral infarction (ACI) and the mechanisms. Ninety ACI patients were randomly divided into control group and observation groups, 45 cases in each group. The control group was treated with rt-PA intravenous thrombolysis, and the observation group was treated with edaravone on the basis of treatment in control group. The treatment course in two groups was two weeks. The treatment efficacy was evaluated. Before and after treatment, the National Institutes of Health Stroke Scale (NIHSS) and activities of daily living (ADL) scores were assessed, and the blood indexes were determined. Results showed that, after treatment, compared with control group, in observation group the total effective rate was significantly increased (P < 0.05), the NIHSS score was significantly decreased (P < 0.05), the ADL score was significantly increased (P < 0.05), the serum neuron-specific enolase and S-100 beta levels were significantly decreased (P < 0.05), the serum tumor necrosis factor-alpha, interleukin-6 and hypersensitive C-reactive protein levels were significantly decreased (P < 0.05), the serum malondialdehyde and lipid peroxide levels were significantly decreased (P < 0.05), and the serum superoxide dismutase level was significantly increased (P < 0.05). In conclusion, compared with single use of rt-PA, the combined use of edaravone and rt-PA can further reduce the inflammatory response and oxidative stress, thus enhancing the treatment efficacy for ACI patients.