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Protein kinase C (PKC) activation by hyperglycaemia may play an important role in the evolution of diabetic retinopathy and other microvascular complications. The PKC-β inhibitor ruboxistaurin belongs to a new class of drugs and has been studied in several clinical trials in microvascular disease, the outcomes of which are described in this review. Ruboxistaurin exhibits promise as the first oral treatment shown to reduce visual loss and the need for laser treatment for macular oedema in patients with moderate to severe non-proliferative diabetic retinopathy. Copyright © 2007 John Wiley & Sons.