With the in-depth understanding of inflammatory factors and pathological mechanisms of chronic sinusitis with nasal polyps (CRSwNP), it was found that different endotypes can guide the treatment and prognosis of CRSwNP with biologic agents. Studies have shown that IL-5 is one of the signature cytokines of type Th2 immune response and plays a key role in the pathogenesis of CRSwNP. Biologics targeting monoclonal antibodies have been developed for the treatment of this disease. Among them, Mepolizumab (Nucala) is a class of monoclonal antibodies targeting IL-5, which can treat refractory CRSwNP by reducing the level of eosinophils in the blood. This paper reviews Mepolizumab as a biologic agent to treat CRSwNP under the guidance of endotype research on CRSwNP.