To explore the relationship between serum levels of intercellular adhesion molecule-1 (ICAM-1), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) and the prognosis of stroke patients undergoing intravenous thrombolysis with alteplase. Methods A total of 127 patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis with alteplase in the hospital from March 2018 to March 2021 were selected. According to the modified Rankin scale (mRS) score in 90 days after treatment, the patients enrolled were divided into good prognosis group (mRS score≤2, n=81) and poor prognosis group (mRS score＞2, n=46). The general clinical data and serum levels of ICAM-1, CRP and MCP-1 of the two groups were compared. Logistic regression analysis was performed to screen the risk factors affecting the prognosis of patients with AIS. The predictive value of ICAM-1, CRP and MCP-1 for 90d poor prognosis of patients with AIS after thrombolysis was evaluating with the receiver operating characteristic (ROC) curve. Results The incidences of coronary heart disease and atrial fibrillation, and the National Institutes of Health Stroke Scale (NIHSS) scores in the poor prognosis group were higher than those in the good prognosis group (P＜0.05). Serum levels of ICAM-1, CRP and MCP-1 in the poor prognosis group were higher than those in the good prognosis group (P＜0.05). Multivariate logistic regression analysis showed that atrial fibrillation, NIHSS score, ICAM-1, CRP and MCP-1 were independent risk factors affecting the poor prognosis of patients with AIS after intravenous thrombolysis with alteplase (P＜0.05). ROC curve analysis showed that the AUC values of serum ICAM-1, CRP, MCP-1 alone and in combination to predict 90d poor prognosis of patients with AIS after thrombolysis were 0.763, 0.729, 0.808 and 0.844, respectively (P＜0.05). The AUC value, sensitivity and specificity of combined detection to predict poor prognosis were significantly higher than those of each index single detection. Conclusion Increased serum levels of ICAM-1, CRP and MCP-1 are independent risk factors for poor prognosis of stroke patients undergoing intravenous thrombolysis with alteplase. The above results indicate that the three indicators all have certain prognostic value, and combined detection of the three can improve the clinical predictive value