hCLEC-2(human C-type lectin-like receptor-2) is a novel identified typeⅡ transmembrane receptor protein. It is found to be closely associated with virus infection, platelet aggregation, tumor metastasis and signal transduction. To study the biological function of hCLEC-2 and signaling pathways it is involved in, a specific antibody against the extracellular domain of hCLEC-2 was prepared. Then, a pET23b-CRD recombinant plasmid was constructed and transformed into BL21 for protein expression. After the induction with IPTG, hCLEC-2-CRD-His was found to be expressed in the inclusion body. The fusion protein in inclusion body was dissolved in 6 mol/L guanidine hydrochloride, purified using Ni-agarose, refolded and dialyzed against PBS. The purified hCLEC-2-CRD-His was used as an antigen to prepare polyclonal antiserum in rabbits, which was subjected to affinity purification with Protein G Sepharose. The specificity of anti-CRD antibody was identified by Western blot analysis of the ectopic expressed GFP-hCLEC-2 and GFP-CRD in comparison with that of GFP antibody. By using this specific antibody, the endogenous hCLEC-2 was revealed to be down-regulated in human monocyte THP-1 cells treated with PMA and IL-4. This preliminary result suggests a correlation between the expression of hCLEC-2 and the differentiation of monocyte. Collectively, the studies here provide a favorable tool for further investigation of hCLEC-2 associated biological functions.