Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction (CR) in rats that were restricted to 70% of control kcals for 4 weeks and subsequently weight-restored. Measures were taken from rats at 80% (chronically restricted, CR), 90% (partially weight-restored, PR), 100% (fully weight-restored, FR), and after 4 weeks at 100% body weight of controls (extended weight-restored, ER). Plasma insulin and leptin were decreased and ghrelin was increased in CR, as compared to controls. Leptin and ghrelin normalized with weight restoration at PR, FR and ER, however baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 weeks.