Objective:To investigate the effect of S100A16 on weight gain process and development of obesity and obesity related diseases. Methods:Rats aged 8 weeks were randomly divided into normal diet group(NF,n = 10) and high-fat diet group (HF,n = 10) to establish a diet induced obesity (DIO) rat model. After feeding for 14 weeks,intraperitoneal glucose tolerance test (IPGTT) and insulin release test (IRT) were performed in rats. After feeding for 16 weeks,rats were sacrificed and subcutaneous and visceral fat weights were measured. Then,HE staining method was used to observe the degree of liver steatosis,and radiation immunity analysis was used to detect serum biochemical indicators,such as blood sugar,insulin,serum uric acid. Western blot was performed to detect the expression of S100A16 and glucolipid metabolism related protein expression of transcription factors in adipose tissue. Results:The weight and visceral fat of rats in the DIO group were significantly higher than those in the normal group. The serum total cholesterol and uric acid in the DIO group was higher than normal glucose tolerance,and insulin release was lower than that of the normal group. Western blot showed that in liver and fat tissue of the DIO group,S100A16,PPAR-γ and C/EPB-α expression were significantly higher than those of the normal group. Conclusion:High fat diet can increase the expression of S100A16 and related expression of transcription factors;S100A16 over expression can promote lipid production and obesity,and result in a negative impact on insulin release and insulin sensitivity.