Objective We investigated the association between the serum butyrylcholinesterase (BChE) activity and parameters of adiposity, insulin resistance and the serum lipid profile, including the serum levels of triglyceride (TG), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) in Japanese patients with type 2 diabetes and non-diabetic subjects. Patients and Methods A total of 259 Japanese subjects [171 patients with type 2 diabetes (age 60.4 +/- 11.9 years, BMI 25.0 +/- 4.4) and 88 non-diabetic subjects (age 54.2 +/- 15.0 years, BMI 25.8 +/- 4.7)] were enrolled in the study. To assess the hepatic fat content, the ratio of the CT attenuation value of the liver to that of the spleen (L/S ratio) was calculated. Results Serum BChE activity was significantly correlated with various indices of adiposity, including the waist circumference, L/S ratio, visceral fat area (VFA), subcutaneous fat area (SFA) and BMI, and also with the TG, HDL-C, LDL-C and HOMA-R, in the entire subject population. Even after adjustment for five variables, namely, age, gender, HbA1c, CRP and serum ferritin ( the serum levels of ferritin and CRP have been reported to be associated with adiposity and insulin resistance), the serum BChE activity was still correlated with the waist circumference, L/S ratio, VFA, SFA, BMI, TG, HDL-C, LDL-C and HOMA-R. Furthermore, changes in the serum BChE activity were associated with changes in the L/S ratio, VFA and SFA at 1 year after the baseline. Conclusions These results indicate that the serum BChE activity is associated with parameters of adiposity, the serum lipid profile and the degree of insulin resistance.