This study examined the possible effects of lycopene at physiological dosage and body fat mass on the humoral immune response in patients with type 2 diabetes mellitus (T2DM). A total of 35 patients with Typ2 diabetes mellitus from both sexes aged 54+/-9 yrs from the Iranian Diabetes Society were introduced into a double blind placebo controlled clinical trial conducted for 2 months. After a 2-week lycopene free diet washout period, patients were allocated to either lycopene supplementation group (10mg/d) (n=16) or placebo age- and sex matched group (n=19) for 8 weeks. Patients were instructed to keep their diets and physical activities as unchanged as possible. Lycopene supplements increased serum lycopene levels (p<0.001). While intake of dietary energy and nutrients did not change in either groups, the ratio of total antioxidant capacity to malondialdehyde increased significantly in the lycopene group (p=0.007). There was an inverse correlation between serum levels of lycopene and those of IgG (r= -0.338, p=0.008). On the contrary, changes of serum levels of lycopene directly correlated with those of IgM (r=0.466, p=0.005). Interestingly, changes of the amount of fat mass correlated directly with those of serum IgG (r=0.415, p=0.044) but inversely with of serum IgM (r= -0.469, p=0.021). While truncal fat might promote adaptive humoral immunity, lycopene probably by inhibiting MDA-LDL formation might attenuate T cell dependent adaptive (pro-atherogenic) humoral immune response. These findings may have preventive implications in long term diabetic complications, notably atherogenesis.