Abstract: Protein tyrosine phosphatase 1B(PTP1B), a member of protein tyrosine phosphatases(PTPs), plays a key role in the negative regulation of insulin and leptin signalings. Recent studies showed that PTP1B had an important connection with endoplasmic reticulum(ER)stress, pancreatic beta cells proliferation and insulin secretion, and is closely related to the pathological process of type 2 diabetes mellitus(T2DM)and obesity. Therefore, PIP1B targeted inhibitors have become a research hotspot in the treatment of these metabolic diseases. Based on the structural features of PTP1B and its relationship with T2DM and obesity, PTP1B inhibitors were classified according to the sites of binding. Their latest research advances were reviewed in this paper, providing a reference for the development of anti-T2DM and anti-obesity drugs targeting PTP1B.