Fibroblast growth factor 21 has recently discovered its pivotal role in glucose, lipid metabolism and regulation of energy homeostasis. Further, it has helped in forming great strides for treatment of chronic diseases like diabetes and inflammation. FGF-21 was sub-cloned into the SUMO vector and was induced for expression in Escherichia coli Rosetta. The recombinant plasmid was transformed into Escherichia coli strain. FGF-21 was induced by IPTG and purified by Ni-NTA agarose (Nickel-nitrilotriacetic acid) column. The purified fusion protein was cleavaged by SUMO protease I to obtain recombinant FGF-21 with high purity. The purified protein was tested for its biological activity of FGF-21. HepG2 cell model was used to detect the regulation of glucose uptake activity of FGF-21 and were further treated with different concentrations of FGF-21.The residual glucose content in medium was measured using the glucose oxidase-peroxidase method. The results indicated that FGF-21 protein had a role in regulating the glucose uptake on HepG2 cells and the effect was significantly dose-dependent manner. In order to further verify whether purified FGF-21 protein obtained has biological activity in diabetic model. Studies have demonstrated that FGF-21 had a greater efficacy in dropping blood glucose in streptozotocin induced diabetic mice.