Keratinocyte growth factor-2 (KGF-2) plays an important role in vertebrate limb development, lung branching morphogenesis, regeneration and reconstruction of the epidermis. Previous studies have used the wild type factor. Here, we have constructed a double-site mutant of human KGF-2, named STEA. STEA possesses higher receptor binding affinity and promotes better proliferation activity on rat tracheal epithelium (RTE) cells than recombinant human KGF-2. These results suggest that the simultaneous mutation of Ser115 to Thr and Glu117 to Ala improves the biological activity of KGF-2.