Leptin is an adipocyte-secreted hormone that regulates weight centrally and regulates food intake and energy metabolism which is present in breast milk and thus may be involved in body composition and differences between breast feeding (BF) and formula-fed (FF) infant. Also there's independent associated between activation of the tumor necrosis factoralpha (TNF-α) and leptin levels that suggest that TNF-α can directly induce leptin gene expression in humans. Subjects and Methods: this study included 47 infants aged (2-24 months) they were 28 male and 19 females infant, exclusive BF was present in 27 of them and the rest were FF, beside full clinical examination and anthropometric measurements (weight (wt), length, head circumference (HC), body mass index (BMI), surface area, skin fold thickness) and full blood count, cholesterol, triglyceride, High density lipoprotein (HDL-C), and low density lipoprotein (LDL-c) , .also serum leptin and TNF-α are measured. Results: BF infant showed significantly higher length /age ratio than FF. Also BF infants showed significantly higher level of serum leptin than FF (2.96ng/ml ±2.8, 1. versus 45ng/ml±1.29), in the other hand there's significant decrease in the mean level of TNF-α in the BF than FF (15.8pg/ml±1.8 versus 17.18pg/ml ±1.75). From these results, it could be concluded that the presence of cytokines and leptin in human milk suggest that the proinflammatory cytokines (TNF-α)and leptin may mediate putative differential anorectic responses of BF and FF infants.