The B6-hIL1RL1 mouse is a humanized model constructed using gene editing technology, where the mouse IL1RL1 signal peptide and endogenous extracellular domain (aa.1~332) were replaced with the human IL1RL1 signal peptide and extracellular domain (aa.1~328). The murine IL1RL1 transmembrane and cytoplasmic region (aa.333~567) were preserved. Homozygous B6-hIL1RL1 mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of cancer, inflammatory, and immune-related diseases, and for the development of IL1RL1-targeted drugs.