This study aimed to explore the effect of intravenous thrombolysis with alteplase on clinical efficacy, inflammatory factors, and neurological function in patients with acute cerebral infarction. A total of 120 patients with acute cerebral infarction were divided into two groups by the random number table method, with 60 patients in each group: observation group (intravenous thrombolysis with alteplase) and control group (intravenous thrombolysis with batroxobin). The clinical efficacy after a 14-day treatment was observed. Serum C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), CD62p, GMP-140, and neuron-specific enolase (NSE) were measured. Scores of National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) were determined. The total effective rate in the observation group was 81.67%, which was higher than the 61.67% in the control group (P<0.05). The improvement of inflammatory factors (CRP, TNF-α, IL-6, CD62p, GMP-140, and NSE), NIHSS, MMSE, and MoCA in the observation group was superior to that in the control group (all P<0.05). The modified Rankin scale at three months after hospital discharge in the observation group was lower than that in the control group (P<0.01). Intravenous thrombolysis with alteplase for acute cerebral infarction can enhance the clinical efficacy, alleviate inflammatory response and brain injury, and improve cognitive function, which is worthy of further clinical application and study.