FGF21 (fibroblast growth factor 21) is a recently described member of the FGF family.  It has been previously demonstrated that FGF21 is a potent regulator of glucose homeostasis.  To improve stability of FGF21 for better efficacy, a new form of recombinant FGF21 was generated by fusion of a full length FGF21 gene and the Fc fragment of human IgG4 with flexible linker sequence.  To examine the glucose regulation activity of FGF21-L-Fc, 3T3-L1 pre-adipocytes were differentiated into adipocytes, and glucose uptake activity of FGF21-L-Fc was examined by glucose oxidase and peroxidase (GOD-POD) assay.  The results showed that in comparison with wild type FGF21, FGF21-L-Fc was more potent in stimulation of glucose uptake by 3T3-L1.  In vivo studies on the modified protein demonstrated that FGF-L-Fc had a better efficacy in lowering blood glucose of the STZ-induced diabetic animals and controlled glucose level for a longer time.  The results provided a sound basis for further studies.