Post-stroke depression （PSD） is a common complication of acute cerebral infarction （ACI）， and alteplase （recombinant tissue plasminogen activator， rt-PA） intravenous thrombolysis is an important treatment regimen for ACI. Recent studies have shown that rt-PA intravenous thrombolysis may be negatively correlated with the incidence rate and severity of PSD after ACI. The mechanisms of action of rt-PA intravenous thrombolysis may include elevated brain-derived neurotrophic factor in the brain and peripheral blood， improved neurological function， and “downward counterfactual thinking”. This article analyzes and summarizes the correlation of rt-PA intravenous thrombolysis with PSD after ACI and its mechanism of action.