Objective: To explore the effects of serum D-dimer (D-D) and the ratio of mean platelet volume to platelet count (MPV/PLT) expression on hemorrhagic transformation (HT) after intravenous thrombolysis with alteplase (rt-PA) in acute cerebral infarction (ACI). Method: Sixty patients with ACI admitted to our hospital from December 2021 to December 2024 were retrospectively collected and included in the observation group. Another 60 healthy individuals who underwent physical examinations in our hospital during the same period were selected and included in the control group. Detect and compare the levels of D-D and MPV/PLT between the two groups. The occurrence of HT in ACI patients after thrombolysis was statistically analyzed. According to the occurrence status of HT, the observation group was further divided into the occurrence group and the non-occurrence group. Collect baseline data for the comparison group and the non-occurrence group. The Logistic regression model was used to analyze the relationship between serum D-D, MPV/PLT and the occurrence of HT after intravenous thrombolytic therapy with rt-PA in ACI patients. Result: The levels of serum D-D and MPV/PLT in the observation group were significantly higher than those in the control group (P < 0.05). Among 60 patients with ACI who received intravenous thrombolytic therapy with rt-PA, 17 cases developed HT within 24 hours, with an incidence rate of 28.33%, while the remaining 43 cases did not develop HT. There were no significant differences in general data such as age, gender and BMI in the occurrence group (P > 0.05). ; The time from onset to medical consultation in the occurrence group was significantly longer than that in the non-occurrence group, and both D-D and MPV/PLT were significantly higher than those in the non-occurrence group (P < 0.05). The analysis results of the Logistic regression model showed that the long time from onset to treatment and the high expression of D-D and MPV/PLT were all influencing factors for the occurrence of HT after intravenous thrombolysis with rt-PA in ACI patients (P < 0.05). Conclusion: The occurrence of HT after intravenous thrombolysis with rt-PA in ACI patients is related to the abnormal expression of serum D-D and MPV/PLT. The abnormally elevated expression of both indicates a high risk of HT after intravenous thrombolysis.