Objective ANGPTL8 is a liver and adipose tissue produced protein that regulates the level of triglyceride in plasma as well as glucose homeostasis. This study was designed to evaluate the level of ANGPTL8 in obese and non-obese subjects before and after exercise training. Methods A total of 82 non-obese and 62 adult obese were enrolled in this study. Subjects underwent a three months of exercise training. Both full length and C-terminal 139â€"198 form of ANGPTL8 were measured by ELISA. Results Our data show that the full length ANGPTL8 level was increased in obese subjects (1150.04 Â± 108.10 pg/mL) compared to non-obese (775.54 Â± 46.12) pg/mL (p-Value = 0.002). C-terminal 139â€"198 form of ANGPTL8 was also increased in obese subjects 0.28 Â± 0.04 ng/mL vs 0.20 Â± 0.02 ng/mL in non-obese (p-value = 0.058). In obese subjects, the levels of both forms were reduced after three months of exercise training; full length was reduced from 1150.04 Â± 108.10 pg/mL to 852.04 Â± 51.95 pg/mL (p-Values 0.015) and c-terminal form was reduced from 0.28 Â± 0.04 ng/mL to 0.19 Â± 0.03 ng/mL (p-Value = 0.058). Interestingly, full length ANGPTL8 was positively associated with fasting blood glucose (FBG) in non-obese (r = 0.317, p-Value = 0.006) and obese subjects (r = 0.346, p-Value = 0.006) C-terminal 139â€"198 form of ANGPTL8 on the other hand, did not show any correlation in both groups. Conclusion In conclusion, our data demonstrate that ANGPTL8 was increased in obesity and reduced after exercise training supporting the potential therapeutic benefit of reducing ANGPTL8. The various forms of ANGPTL8 associated differently with FBG suggesting that they have different roles in glucose homeostasis.