Objective: To explore the relationship between expression of coiled-coil domain-containing protein 80(CCDC80) and obesity in serum and adipose tissues., Methods: A cross-sectional survey was conducted in a hospital in Tangshan in September 2010. 100 people including 78 healthy people and 22 with type-2 diabetes were recruited. Another 36 female patients with benign tumor of Obstetrics and Gynecology were also recruited. Demographic characteristics and serum samples were collected from all subjects, basic biochemical indicators were tested. All subjects were divided into 'Normal Weight' and 'Overweight and Obese' according to their BMI (BMI <24.0 kg/m(2); BMI≥24 kg/m(2)). Serum CCDC80 of the 100 subjects was detected by ELISA. Visceral and subcutaneous fat were derived from the other 36 female subjects, and Real-time PCR was used to detect CCDC80 mRNA expression in adipose tissues. Pearson correlation and multiple linear regression were used to analyze the correlation between serum or adipose CCDC80 expression and waist, BMI, and other biochemical indicators., Results: The age of 100 subjects was (52.9±8.4) years old. 44% of them were women (44 cases) and 56% of them were men (56 cases). After dividing them into three groups according to their BMI, covariance analysis were conducted, and age and gender were adjusted. The HDL-C level was significantly different among three groups (F = 10.73, P < 0.001): 'Overweight and obese combined with diabetes' group ((0.90±0.06) mmol/L)< 'Overweight and obese' group ((1.14±0.04) mmol/L) < 'Normal weight' group ((1.28±0.05) mmol/L). The adjusted expression of serum CCDC80 of the 100 subjects was (5.84±0.16) pg/ml, (5.81±0.98) pg/ml among men and (5.97±0.89) pg/ml among women, and there was no significant difference (t = -0.812, P = 0.419) between genders. ANOVA revealed that there was no significant differences of the expression of serum CCDC80 among three groups (F = 1.06, P = 0.351), 'Normal weight' group was (5.84±0.16) pg/ml, 'overweight and obese' group was (6.11±0.14) pg/ml, and 'Overweight and obese combined with diabetes' group was (5.84±0.19) pg/ml. The analysis showed that FBG had a negative correlation with serum CCDC80 (R(b) = -0.223, P = 0.026). Multivariate linear regression had a similar result, with 1 mmol/L increase of serum FBG, serum CCDC80 decreases for 0.24 pg/ml (β = -0.24, 95% CI: -0.21--0.02). There was also a negative correlation between serum CCDC80 and FBG in overweight and obese people (R(a) = -0.368, P = 0.013). Besides, CCDC80 mRNA was detected in both subcutaneous and visceral adipose tissue of 36 cases, the expression level was 0.06±0.02 for subcutaneous fat, was 0.05±0.04 for visceral fat, and the expression in visceral fat was lower (0.05±0.03) than that in subcutaneous fat (0.06±0.03) (t = 2.50, P = 0.025) among overweight and obese group. There was a negative correlation between waist and visceral CCDC80 mRNA expression (r = -0.472, P = 0.035)., Conclusion: This study suggested that CCDC80 may be involved in energy and insulin metabolism, and plays a protective role in obesity and diabetes.