Objective：To study the functions of the first extracellular domain of β chemokine receptor 5(CCR5) NH2-terminal and to prepare its specific antibody F(ab′)2. Methods: Some β chemokine superfamily members were analyzed by computer and the least homologous domain of the extracellular loops were located. The first extracellular domain 114 nucleotides fragment was defined, sequenced and amplified by PCR，the expression vector pGEX-IN/NR5 of a recombinant GST fusion protein was constructed. After confirming the correctness of the inserted sequence，the transformation and expression of this fusion protein were performed in E. coli. The expression products of the fusion protein were purified and 2 New Zealand rabbits were immunized. An anti-CCR5 NH2-terminal antibody F (ab′)2 was prepared by protein A affinity chromatography，pepsin digestion and Sepharose-12 column chromatography. Results： Reduced, unreduced SDS-PAGE and FAX analysis demonstrated that this F (ab′)2 had high specificity to combine with CCR5. Conclusion：In this paper，we introduce a simple and quick method to get a specific antibody F (ab′)2 of certain functional domain. By that，not only can we get an important experiment material for studying gene expression，but also a good idea and technique to study other high similar superfamily members.