Aging is often associated with overweight and obesity. There exists a long-standing debate whether meal pattern also contributes to the development of obesity. The orexigenic hormone ghrelin regulates appetite and satiety by activating its receptor, growth hormone secretagogue receptor (GHS-R). In mice, circulating ghrelin levels and brain GHS-R expression have been shown to increase with aging. To assess whether GHS-R regulates feeding pattern during aging, we studied meal patterns for the following cohorts of male mice fed a normal chow diet: young wild-type (WT) mice (3-4 months, WT-Y), young Ghsr-null (Ghsr-/-) mice (3-4 months, Ghsr-/--Y), middle-aged WT mice (12-14 months, WT-M), middle-aged Ghsr-/- mice (12-14 months, Ghsr-/--M), old WT mice (24-26 months, WT-O), and old Ghsr-/- mice (24-26 months, Ghsr-/--O). Even though the total daily food intake of Ghsr-/- mice was similar to that of WT controls, Ghsr-/--M and Ghsr-/--O mice had 9% (P = 0.07) and 16% (P < 0.05) less body weight compared with WT-M and WT-O mice respectively, primarily due to reduced fat mass (P < 0.05, WT-M vs. Ghsr-/--M and WT-O vs. Ghsr-/--O). Intriguingly, Ghsr-/--M mice ate larger meals (on average, Ghsr-/--M ate 0.117 g/meal and WT-M ate 0.080 g/meal, P < 0.01), took longer time to eat (Ghsr-/--M: 196.0 s and WT-M: 128.9 s, P < 0.01), but ate less frequently (Ghsr-/--M: 31.0 times/day and WT-M: 42.3 times/day, P < 0.05) than did WT-M controls. In addition, we found that expression of hypothalamic orexigenic peptides, neuropeptide Y (NPY) and agouti-related peptide (AgRP), was relatively lower in aged WT mice (P = 0.09 for NPY and P = 0.06 for AgRP), but anorexic peptide pro-opiomelanocortin (POMC) expression levels remained unchanged between WT age groups. Interestingly, old Ghsr-/- mice had greater hypothalamic NPY expression (102% higher, P < 0.05) and AgRP expression (P = 0.07), but significantly lower POMC expression (P < 0.05), when compared with age-matched WT-O controls. Our results thus indicate that GHS-R plays an important role in the regulation of meal pattern, and that GHS-R ablation may modulate feeding behavior through the regulation of hypothalamic neuropeptides. Our results collectively suggest that ghrelin receptor antagonism may have a beneficial effect on metabolism during aging.