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Protein tyrosine phosphatase-1B (PTP1B) is an important negative regulator of insulin receptor– and vascular endothelial growth factor receptor–dependent signalings in endothelial cells. Genetic or pharmacological inhibition of PTP1B has been shown to enhance endothelial cell proliferation and migration and increase nitric oxide production. In vivo, inhibiting PTP1B can reverse endothelial dysfunction, promote angiogenesis, and accelerate wound healing. Intense research is currently continuing in an effort to discover novel selective PTP1B inhibitors, primarily for treating insulin resistance. We propose that these drugs may also represent a new horizon for boosting the regenerative capacities of endothelial cells.