Progranulin (PGRN) encodes a 68.5-kDa secreted growth factor that is composed of seven and a half tandem repeats of a 12-cysteine granulin motif. PGRN is expressed in many tissues and has a role in mediating development, wound repair, inflammation, and tumorigenesis. Mutations leading to a loss of function in PGRN are the most common cause of familial frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP). In this study, we established hybridoma cell lines producing antibodies against human PGRN. Murine monoclonal antibodies (MAbs) against human PGRN were generated by using purified eukaryotic recombinant PGRN-6His fusion protein as immunogen. A panel of seven monoclonal antibodies was obtained after the preliminary screening by indirect enzyme-linked immunosorbent assay (ELISA), the data of which was confirmed by Western blot analysis and immunocytochemistry. By using constructs expressing a series of C- and N-terminal truncations, and single domains of PGRN, the particular domains recognized by MAbs were also identified. Domain-specific anti-PGRN MAbs will be an essential tool for investigating the role of PGRN in normal physiological or pathological conditions.