Purpose To report the biologic effect of intravitreal bevacizumab in patients with retinal and iris neovascularization secondary to diabetes mellitus. Design Interventional, consecutive, retrospective, case series. Participants Forty-five eyes of 32 patients with retinal and/or iris neovascularization secondary to diabetes mellitus. Methods Patients received intravitreal bevacizumab (6.2 μg–1.25 mg). Ophthalmic evaluations included nonstandardized Snellen visual acuity (VA), complete ophthalmic examination, fluorescein angiography, and optical coherence tomography. Main Outcome Measures Change in fluorescein angiographic leakage of the proliferative diabetic retinopathy (PDR). Secondary outcomes included changes in Snellen VA. Results No significant ocular or systemic adverse events were observed. All patients with neovascularization demonstrated by fluorescein angiography (44/44 eyes) had complete (or at least partial) reduction in leakage of the neovascularization within 1 week after the injection. Complete resolution of angiographic leakage of neovascularization of the disc was noted in 19 of 26 (73%) eyes, and leakage of iris neovascularization completely resolved in 9 of 11 (82%) eyes. The leakage was noted to diminish as early as 24 hours after injection. In addition to the reduction in angiographic leakage, the neovascularization clinically appeared to involute in many patients with a reduction in the caliber or presence of perfused blood vessels. In 2 cases, a subtle decrease in leakage of retinal or iris neovascularization in the fellow uninjected eye was noted, raising the possibility that therapeutic systemic levels were achieved after intravitreal injection. Recurrence of fluorescein leakage varied. Recurrent leakage was seen as early as 2 weeks in one case, whereas in other cases, no recurrent leakage was noted at last follow-up of 11 weeks. Conclusions Short-term results suggest that intravitreal bevacizumab is well tolerated and associated with a rapid regression of retinal and iris neovascularization secondary to PDR. A consistent biologic effect was noted, even with the lowest dose (6.2 μg) tested, supporting proof of concept. The observation of a possible therapeutic effect in the fellow eye raises concern that systemic side effects are possible in patients undergoing treatment with intravitreal bevacizumab (1.25 mg), and lower doses may achieve a therapeutic result with less risk of systemic side effects. Further study is indicated.