Objective To investigate the association of rs7566605 polymorphism in the insulin-induced gene 2 (INSIG2) with obesity and lipid metabolism in Chinese elderly. Methods A total of 742 elderly receiving 2 surveys conducted during the years of 2001 and 2010 were subjected and longitudinally analyzed. All participants were asked to complete the health questionnaires and genotyping. The changes in body mass index (BMI), fasting blood glucose and blood lipid levels between the twice examinations were observed. The effects of aging and genetics on lipid metabolism were analyzed in the cohort. Moreover, the association between the rs7566605 genotypes with obesity and dyslipidemia, including hypercholesterolemia, hypertriacylglycerolemia or low high-density lipoprotein cholesterol (HDL-C) was analyzed with a variety of genetic models. Results Besides BMI, serum levels of fasting blood glucose, triglycerides (TG), HDL-C and the value of systolic blood pressure were increased in both male and female subjects during the 10 years. Serum total cholesterol was increased in the males but decreased in the females. Based on the data of 2001, the serum levels of fasting blood glucose and TG were higher in the males with allele C than with GG, while the females with allele C had lower level of HDL-C. No association was found between the rs7566605 genotypes with obesity. Logistic regression analysis indicated that allele C increased the risk of lower HDL-C (dominant model: P＝0.011, OR＝1.726; heterogeneous codominant model: P＝0.002，OR＝1.890), while it showed a protective effect on hypercholesterolemia (dominant model: P＝0.008, OR＝0.601; additive model: P＝0.040, OR＝0.753; heterogeneous codominant model: P＝0.015, OR＝0.634). Conclusion INSIG2 gene rs7566605 polymorphic allele C is associated with serum lipid metabolism in Chinese elderly population. Dominant and heterogeneous codominant model might be main genetic models for the gene.