Apolipoprotein E (apo E) polymorphism has been reported to influence some lipid profile abnormalities in some ethnic groups. This study was conducted mainly to examine the possible association of apo E polymorphism with overweight/obesity in a South West Chinese population. Four hundred and fifty-four Han Chinese (282 overweight/obese and 172 normal weight control subjects) in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The genotype and allele frequencies of apo E polymorphism in cases of overweight/obesity showed no significant statistical difference compared to those of controls. In the control group, both apo E4 and E3 allele carriers had the higher serum LDL-C and lower triglycerides (TGs) and apo E concentrations than those with apo E2 carriers, while apo E2 allele carriers had higher serum apo C-II levels than apo E3 carriers (P < 0.05). In overweight/obese group, genotype-related low density Lipoprotein-Cholesterol (LDL-C) variations were also evident, with the changes being in a same direction as the effect in the controls, and apo B100 levels were decreased and apo E increased in apo E2 allele carriers when compared with respective apo E4 and apo E4/apo E3 allele carriers (all P < 0.05). Polymorphism of the apo E gene is associated with altered plasma LDL-C and TG, as well as apo B, apo C-II, and apo E concentrations. The effects on TG, apo B, and apo C-II levels are BMI dependent in Chinese population of Chengdu area.