OBJECTIVE To investigate the relationship among fasting serum free fatty acid (FFA), insulin sensitivity index (ISI), serum triglyceride (TG) and total cholesterol (TC) levels in subjects with different body mass index (BMI) and glucose tolerance by using Bergman's minimodel method. METHODS 26 normal control subjects, 39 obese subjects, 25 impaired glucose tolerance (IGT) subjects and 21 patients with newly diagnosed type 2 diabetes mellitus (DM) were recruited into this study. Serum FFA level was measured with radioimmunoassay and ISI was obtained by using Bergman's minimal model method. RESULTS (1) In the four groups, serum FFA concentration of the control group was significantly lower than that of the other three groups, although there was no difference among the latter three. (2) ISI level of the control group was significantly higher than that of other three groups, while there was no difference among the latter three. (3) After adjusting with BMI, there was still significant difference in serum FFA levels between the control and the other three groups. (4) ISI, HOMAIR, BMI, waist hip ratio (WHR) and TG were all related to the concentration of serum FFA (r = -0.454, 0.213, 0.241, 0.336 and 0.414 respectively, P < 0.01, < 0.05, < 0.05, < 0.01 and < 0.01 respectively), while age, sex and serum TC levels were not related with serum FFA. (5) According to multivariate stepwise regression, ISI, BMI and TG were the major determinant factors for FFA (R(2) = 0.109, 0.212, 0.156, P < 0.001). CONCLUSIONS Besides BMI, ISI and serum TG level are the major determinant factors that affect the concentration of serum FFA. As compared with the simple index HOMAIR, ISI level was more significantly related with serum FFA concentration. FFA levels are significantly different in various glucose tolerant states even after adjusting with BMI. FFA levels were obviously higher in subjects with IGT or type 2 diabetes mellitus.