Objective To investigate the efficacy and the safety of external therapy of ultrasound (ETUS) enhancing thrombolysis on the experimental retinal vein occlusion. Methods The effect of ETUS enhanced thrombolysis and the impact of ultrasound energy and exposure were investigated respectively after both eyes of 51 rabbits with retinal branch vein occlusion created by photodynamic initiated thrombosis were divided into 4 groups. The first 2 groups are the ETUS groups, including one group (15 rabbits) underwent intravenous injection with urokinase (UK) (1700-2200 UK dissolved into 20 ml normal saline), and other group (12 rabbits) underwent intravenous injection with normal saline. In these 2 groups, each rabbit received ETUS treatment (1.0 W/cm2, 20 min) in one eye and the fellow eye did not which was as the control. The latter 2 groups are the energy and duration of ultrasound groups, and 12 rabbits in each group underwent ETUS with the energy of 0.7 and 1.0 W/cm2 respectively. Each of the 2 groups was divided into 3 subgroups (8 rabbits in each) according to the radiated durations (8, 14, and 20 minutes). All of the eyes except the control ones underwent ETUS with 1 MHz ultrasound and 100 Hz pulsed ultrasound once a day for 3 days. Fundus fluorescein angiography (FFA) was used to detect the vascular condition 4 days after ETUS, and at the 15th day, retinal light microscopy and electron microscopy were performed. Results The vascular recanalization rate in ETUS+UK treatment group was 66.7%, which is obviously higher than which in single UK group (20.0%, P=0.025), normal saline group (8.3%, P=0.005), and ETUS+ normal saline group (8.3%, P=0.005). The vascular recanalization rates in groups with different energy of ultrasound increased obviously as the radiated durations increased (P=0.006, 0.001), while no apparent effect of energy of ultrasound on the vascular recanalization rate was found in the groups with different radiated duration (Pgt;0.05). The eyes which had undergone ETUS treatment had retinal tissue damage and ultrastructure changes of the retinal ganglion cells (RGC), and deteriorated as the radiated duration increased. Conclusion ETUS may enhance the thrombolysis induced by urokinase in experimental retinal vein occlusion. Simultaneously, ETUS can lead to the damage of retinal tissue and changes of the ultrastructure of RGC. (Chin J Ocul Fundus Dis, 2007, 23: 166-169)