Low birth weight and catch-up growth predict increased adiposity in children and adults. This may be due in part to leptin resistance, as adults who were born small exhibit increased plasma leptin concentration relative to adiposity. Placental restriction (PR), a major cause of intrauterine growth restriction, reduces size at birth and increases feeding activity and adiposity by 6 wk in sheep. We hypothesized that PR would increase plasma leptin concentration and alter its relationship with feeding activity and adiposity in young lambs. Body size, plasma leptin, feeding activity, adiposity, leptin, and leptin receptor gene expression in adipose tissue were measured (12 control, 12 PR). PR reduced size at birth and increased adiposity. Plasma leptin concentration decreased with age, but to a lesser extent after PR and correlated positively with adiposity similarly in control and PR. PR increased plasma leptin concentration and perirenal adipose tissue leptin expression. Feeding activity correlated negatively with plasma leptin concentration in controls, but positively after PR. PR increases adipose tissue leptin expression and plasma leptin concentration, however, this increased abundance of peripheral leptin does not inhibit feeding activity (suckling event frequency), suggesting PR programs resistance to appetite and energy balance regulation by leptin, leading to early onset obesity. ; Miles J. De Blasio, Dominique Blache, Kathryn L. Gatford, Jeffrey S. Robinson and Julie A. Owens