Objectives: -This study examines the effect of two different antiangiogenic drugs (rapamycin and thalidomide) in prevention of neovascularization when locally used, after laser coagulation through dorsal skinfold window chamber rat model. - Determine what is the most effective antiangiogenic drug when used locally and its potential side effects. Methodology: The study includes 3 groups, each group contains 10 rats Thalidomide, Rapamycin and control group (laser group). Blood vessels in the dorsal window chambers implanted on dorsal skin of albino rats were irradiated by Diode laser pulses until coagulation occurs. Blood flow and vessels structure were documented with high definition camera to evaluate photocoagulation and reperfusion. Treatment groups received the treatment drug which was injected to the widow’s medial side, every 3 days’ intervals for 2 weeks after laser irradiation. Results: Control group, 26 out of 28 photocoagulated blood vessels reperfused within 5-12 days with reperfusion rate about 93%, in Rapamycin group the reperfusion rate was about 46%. We also found that the reperfusion rate in Thalidomide group was about 8% which was the lowest reperfusion rate in all groups. Conclusions: Thalidomide group reperfusion rate was about 8% which was the lowest reperfusion rate in all groups. Thalidomide is more effective than Rapamycin, and it`s antiangiogenic effect lasts for weeks with no side effects detected with local use.