Tissue plasminogen activator (t-PA), a serine protease capable of promoting fibrin degradation and thrombus dissolution, plays a pivotal role in the management of cardiovascular and cerebrovascular diseases. In recent years, its ophthalmic applications have expanded significantly. Intravitreal administration of t-PA demonstrates efficacy in inducing posterior vitreous detachment, thereby enhancing surgical success rates. Combined application with vitrectomy markedly improves outcomes in subretinal hemorrhage management. Systemic thrombolysis via intravenous or intra-arterial routes effectively alleviates central retinal artery occlusion, while suprachoroidal injection facilitates resolution of suprachoroidal hemorrhage. Notably, the synergistic effect of subretinal co-administration with anti-vascular endothelial growth factor agents enhances anti-angiogenic efficacy, offering novel therapeutic strategies for ocular neovascular disorders. In the future, it is necessary to further clarify the best indication of t-PA, improve the treatment scheme, and explore the combined application with other treatment methods to promote the innovation of ophthalmic treatment.