Problem statement: Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a liver serine protease that regulates LDL cholesterol metabolism (Seidah et al. 2014). PCSK9 binds to LDL receptors, and guides them to lysosomes, where they will be degraded. In the absence of LDL receptors, liver cannot anymore bind the LDL, and the level of circulating LDL cholesterol increases. The aim of the study was to measure the plasma PCSK9 concentrations in prediabetic subjects with or without statin treatment and its association between PCSK9 and physical activity. Methods: 67 subjects with high risk of type 2 diabetes were recruited to a 3-month intervention to achieve moderate physical activity registered by an accelerometer. Blood samples were collected at baseline and after intervention for analysis of PCSK9 and lipid biomarkers. Univariate analysis was used to assess the statistical significances. Results: The mean number of daily steps was 5870 ± 3277 in the intervention group and 4034 ± 3460 in the control group at the acceleration levels 1.3 -1.7 g (p<0.029). At baseline statin treated subjects had higher plasma PCSK9 levels and total cholesterol was positively correlated with plasma PCSK9 (R=0.320, p=0.008), while maximal oxygen uptake was negatively associated (R=-0.252, p=0.044). After the 3 months physical activity intervention plasma PCSK9 levels were positively correlated with HDL cholesterol (R=0.264, p=0.030), while maximal oxygen uptake was even stronger inversely associated (R=-0.410, p=0.0008). Interestingly, plasma PCSK9 levels were higher in April than in January. Conclusion: The physical activity by our subjects with high risk for type 2 diabetes did not influence plasma PCSK9 levels. Higher physical activities might be more effective in reducing PCSK9 levels, but our prediabetic subjects were not able to increase their physical activity further.