Neovascular diseases are the leading causes of blindness in humans. Although several promising compounds have been isolated, pharmacological treatment remains difficult. Thalidomide has inhibitory effects on angiogenesis in the corneal micropocket assay. However, the results vary considerably depending on the administration route and animal model. The aim of this study, therefore, was to investigate thalidomide and two of its derivatives, supidimide and EM12, in the rabbit corneal micropocket assay. Using both basic fibroblast growth factor and vascular endothelial growth factor for initiation of the neovascular response, we were able to show a significant inhibition of neovascularisation with all three substances. EM12, the most teratogenic derivative analysed, was demonstrated to be the most potent inhibitor of angiogenesis in this model. Thalidomide and supidimide did not show systemic side effects in the applied dosage. An equal dosage of EM12, however, resulted in significant weight loss of the animals, but did not increase angiogenic activity compared with lower doses. Together with earlier findings, these data support a strong correlation between the antiangiogenic potential and the teratogenic activity of thalidomide and structurally related compounds.