To obtain recombinant glial cell line-derived neurotrophic factor receptor alpha1 (GFRα1) and study its biological activity, the cDNA encoding the mature rat GFRα1 was isolated using RT-PCR with total RNA extracted from newborn SD-rat hippocampus tissue. The expression plasmid pET-GFRα1 was constructed by inserting GFRα1 cDNA into plasmid pET-28a(+) containing T7 promoter and transformed into E.coli BL21(DE3).An expression strain BLGFRα1 was selected.SDS-PAGE analysis revealed that the rat GFRα1 protein was highly expressed and accumulated up to 21.5% of the total bacterial proteins in the form of inclusion body after the induction. By Ni²⁺ chelation affinity chromatography, up to 90% GFRα1 protein was purified. Purified and refolded GFRα1 protein could significantly mediate the ability of GDNF to promote the survival and induce the differentiation of PC12 cells.