We assessed the effect of glucose and insulin on human monocytes. Monocytes were isolated from 16 healthy obese and 10 lean healthy participants. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. Obese participants were subdivided into 2 subgroups: insulin sensitive (IS) and insulin resistant (IR). Monocyte oxidized low-density lipoprotein (oxLDL) phagocytosis was assessed pre and poststimulation in vitro with glucose or insulin. Experiments were repeated after incubation with a Na(+)/H(+) exchanger-1 inhibitor ([NHE-1]; cariporide) or rosiglitazone. Glucose increased oxLDL phagocytosis in all groups studied (at 1 or 3 hours incubation; P = .037-.002). Insulin increased oxLDL phagocytosis in all groups studied after 1-hour incubation (P = .027-.015) but not at 3 hours. Incubation with cariporide attenuated oxLDL phagocytosis except in the obese IS group. Rosiglitazone eliminated glucose- and insulin-induced increase in oxLDL phagocytosis in all studied groups. Glucose and insulin induce oxLDL phagocytosis.