Aim To explore the possible association between insulin like growth factor Ⅱ receptor (IGF2R) rs9456497 polymorphism and cardiovascular risks in a long-lived population residing Guangxi Hongshui River basin. Methods IGF2R rs9456497 polymorphism was genotyped by iMLDR technique for 496 Zhuang long-lived individuals (long-living group) and their offspring (offspring group, n=723) and matched healthy controls (control group, n=611) living in Hongshui River basin. Association analysis were then conducted among genotypes and blood pressure, body mass index(BMI) and serum lipid levels. Results Overall, no significant difference was detected among genotypes in each group except that the mutant genotype (GA/GG) tended to reduce the SBP and DBP levels (P=0.016 and 0.033, respectively) in longevity group. However, after sex stratification, in males, the total cholesterol (TC) level of each genotype in offspring was elevated as compared with relevant genotype in longevity group and control group (P＜0.05 for each); the triglyceride (TG), fasting plasma glucose (FPG) and BMI levels of each genotype in longevity group were lower while SBP and DBP levels were higher than that of the relevant genotype in offspring and controls (P＜0.05 for each). In females, longevity group tended to display lower TG, FPG and BMI but higher SBP and DBP levels than offspring and controls as in males; intragroup comparison showed that the FPG level of GG/GA genotype was significantly lower than that of AA genotype (P=0.041) in controls while other parameters did not differ across genotypes in each group (P＞0.05 for all). After stratified by lipid status, the frequency of G allele was markedly increased in the dyslipidemic subgroup in the combined population and controls which might imply that A＞G mutation on rs9456497 tend to increase the rate of dyslipidemia; G genotype (GA/GG) greatly lowered the TC and SBP levels in the logevous normolipidemic subgroup, lowered the DBP level of normolipidemic subgroup and the low density lipoprotein cholesterol (LDLC) of the dyslipidemic group but increased the TC level of normolipidemic subgroup in controls. Conclusion IGF2R rs9456497 polymorphism may correlate with the cardiovascular risks to some extent, but its effects on the modulation of these risk factors seem limited, which may be influenced by sex and lipid status.