AIM: To evaluate the role of a single intravitreal injection of tissue plasminogen activator alone (TPA) for treatment of vitreomacular traction and the effect of combined intravitreal TPA and bevacizumab on retinal vascular diseases. METHODS: In this prospective, interventional case series a total of 24 eyes from 24 patients were studied. There were 5 eyes with symptomatic vitreomacular traction syndrome (VMT) and 19 eyes with retinal vascular diseases including diabetic macular edema (DME), diabetic vitreous hemorrhage (VH), central retinal vein occlusion (CRVO) and neovascular age related macular degeneration (AMD). Measurement of visual acuity, B-scan and OCT were performed at the baseline and 1mo after injections. Three eyes with VMT received a single intravitreal injection of 50 μg and two eyes received 100 μg TPA. Totally 19 eyes with retinal vascular diseases received combined intravitreal TPA (50 μg) and Bevacizumab (1.25 mg). RESULTS: The mean ages for retinal vascular diseases and VMT patients were 56.8y and 60.4y, respectively. Ten patients (41.7%) were male and 14 patients (58.3%) were female. 22 eyes (91.7%) were phakic and 2 eyes (8.3%) were pseudophakic. The incidence of posterior vitreous detachment (PVD) was 0% (0 of 5) and 57.8% (11 of 19) for VMT and retinal vascular diseases, respectively (P=0.04). Improvement of best corrected visual acuity (BCVA) and decrement of central macular thickness (CMT) were significantly greater in PVD positive eyes compared with PVD negative eyes. CONCLUSION: Intravitreal injection of TPA was not successful to induce complete PVD in VMT patients. Combined intravitreal injection of TPA and Bevacizumab can induce PVD and improve BCVA and decrease central macular thickness in eyes with retinal vascular diseases.