Leptin, an adipokine secreted by white adipocytes, is known for its function in regulating food intake and energy expenditure, but the mechanisms regulating its circulating levels is not fully understood. Our previous findings suggest that as yet unidentified humoral factors released from enterocytes are involved. The present study tested glucocorticoids (GCs) as candidate factors. Supplementation of corticosterone and cortisol promoted leptin production in murine adipocytes from the 3T3-L1 cell strain and human adipocytes from the Simpson Golabi-Behmel syndrome (SGBS) cell strain, respectively. These changes were observed in the absence but not presence of the GC-receptor antagonist mifepristone. The cortisol concentration in conditioned medium (CM) of human enterocyte-like Caco-2 cells was increased by phorbol-12-myristate 13-acetate and decreased by metyrapone. When SGBS adipocytes were cultured in these CMs, leptin production was positively associated with cortisol concentrations. During a 2-h refeeding after fasting, plasma leptin levels continued to increase in sham-operated mice, transiently increased at 60 min in adrenalectomized mice, and were unchanged in mifepristone-administered mice. These results suggest that extra-adrenal GCs contribute to the GC-receptor signaling-dependent increase of postprandial circulating leptin, whereas further studies will be required to determine whether enterocytes participate in the GCs-mediated increase of postprandial circulating leptin.