Bradykinin is a key mediator of hereditary angioedema (HAE) and we hypothesized it may similarly contribute to edema that is common to retinal disease through its pro-inflammatory and vasodilatory effects. To test the hypothesis, we generated potent inhibitors capable of blocking both B1 and B2 bradykinin receptors to examine their function in peripheral and ocular edema models. First, we observed that subcutaneous administration of a dual bradykinin receptor antagonist (PTGX9) was highly effective at reducing peripheral edema. Second, we found intravitreal administration of dual bradykinin receptor antagonists effectively reduced retinal vascular leakage in the rat laser-induced choroidal neovascularization model that was equal to that of aflibercept-treated rats. Finally, we present a preclinical pharmacokinetic result suggesting the potential for effective monthly or less frequent dosing.