In the mammalian olfactory epithelium (OE), neurogenesis continues throughout the lifetime, by replacing olfactory receptor neurons (ORNs) lost by normal turnover in the postnatal period. However, this ability decreases with age and/or because of various toxic factors. To date, no effective treatment for olfactory dysfunction' especially because of aging, is available in clinical practice. Here, we examined the effects of intranasal administration of fibroblast growth factor-2 and insulin-like growth factor-1 in gelatin hydrogel on the degenerated OE of aging mice induced by methimazole administration. These topical treatments led to increases in the number of olfactory marker protein-positive cells, which identified mature ORNs, resulting in the increased thickness of OE. These results indicate that both fibroblast growth factor-2 and insulin-like growth factor-1 promote the proliferation of basal cells and differentiation of immature ORNs into mature ORNs in the degenerated OE of aging mice. These agents might be promising candidates for the treatment of degenerated OE of aging humans.