B6-hIL4 mice are humanized models generated using gene editing technology by replacing the sequences from the ATG start codon to the TAG stop codon of the endogenous mouse Il4 gene with the sequences from the ATG start codon to the TGA stop codon of the human IL4 gene. Homozygous B6-hIL4 mice are viable and fertile. This model is an invaluable tool for studying allergic diseases (e.g., asthma and atopic dermatitis), Th2 immune responses, parasitic infections, tumor immunology, and chronic inflammation. Furthermore, it serves as a robust preclinical platform for evaluating the efficacy and mechanisms of therapeutic agents targeting the IL-4.