Objective:To observe the clinical efficacy of rt-PA in the treatment of patients with acute ischemic stroke ( CIS) and hyperdense middle cerebral artery sign ( HMCAS) . Methods:Totally 107 patients with CIS and HMCAS were randomly divided into the control group (n=54) and the treatment group (n=53). The control group was treated with urokinase, while the treatment group was treated with recombinant tissue type plasminogen activator ( rt-PA) . The treatment course was 14 days, and then the clinical effi-cacy and safety were evaluated. Results:Compared with that before the treatment, the score of national institute of health stroke scale ( NIHSS) in both groups was decreased after the treatment, and the decrease in the treatment group was more notable than that in the control group with statistically significant difference (P<0. 05). The clinical effective rate of the treatment group was 88. 68%, while that of the control group was 79. 63%, and there was statistically significant difference between the groups (P<0. 05). Compared with that before the treatment, BI index in both groups was increased after the treatment, and the increase in the treatment group was more significant than that in the control group with statistically significant difference (P<0. 05). Conclusion:rt-PA thrombolytic therapy in the patients with CIS and HMCAS has remarkable clinical efficacy, which can improve patients’ life quality and is worthy of promo-tion.