Objective：This study aims to investigate the influence of abrupt fluctuation of blood glucose and insulin on serum PCSK9 level during intravenous glucose tolerance test（IVGTT），and its potential relationship with glucose and lipid metabolism. Methods：IVGTT were detected on 23 healthy lean and 52 patients with obesity or abnormal glucose metabolism. Personal medical history and anthropometry were recorded. Lipid profile，liver function and kidney function were measured in fasting serum samples. Serum PCSK9 levels were detected in serum samples collected during IVGTT at different time points. According to the ratio of serum PCSK9 content between 4 minutes post intravenous glucose challenge and baseline，participants were grouped into the down-regulation group，the stable group and the up-regulation group. Glucose and lipid metabolism parameters were compared across these three groups. Besides，free fatty acids，ceramides and their metabolites in 39 serum samples were determined by high throughput targeting lipidomics. Results：In general，baseline PCSK9 level was positively correlated with total cholesterol and fasting C-peptide level after adjustment，but basal PCSK9 level was not corrected with fasting insulin level. With the increase of blood glucose during IVGTT，insulin increased sharply，accompanied by the fluctuation of serum PCSK9 level. The results showed that the basal PCSK9 and fasting insulin levels in the down-regulation group were significantly higher than those in the stable group and the up-regulation group，and the proportion of prediabetes and diabetes in the down-regulation group was higher. In addition，the serum levels of total ceramide and total glucosylceramide in the down-regulation group were significantly higher than those in the other two groups. The positive correlation between baseline PCSK9 content and CER D18：1/24：0 and GM3 D18：0/24：0 in lipid subclass analysis remained even after adjustment for other factors. Conclusion：During IVGTT，serum insulin level increases sharply along with instant increase in blood glucose，and serum PCSK9 content fluctuates as well. The fluctuation patterns of serum PCSK9 level during IVGTT is related with basal glucose and metabolism status.