Numerous epidemiology reports suggested that consumption of coffee is associated with lower risk of diabetes mellitus (Natella & Scaccini, 2012). These epidemiological observations have not been evaluated experimentally. The present study therefore employs an animal model to examine the relationship between intake of coffee and risk of type 2 diabetes mellitus (in this case, insulin resistance). In the study, high-sucrose feeding (30% w/v) was used to induce insulin resistance (Riberio et al, 2005). Sprague-Dawley rats (male, 120-150g) were maintained for 12 weeks on a normal diet (ND, n=6), normal diet supplemented with coffee (ND+COF, 300 mg/kg BW, n=6), high sucrose-diet (HSD, n=6) and high sucrose-diet supplemented with coffee (HSD+COF, n=6). Glucose tolerance and insulin resistance were measured by performing the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) respectively; and for both tests, the area under curve (AUC) was calculated. Blood sampling was carried out by tail tipping for rats loosely restrained in hand towel for the determination of blood glucose level at intervals of 0, 30, 60, 90, 120 and 180 min. The serum insulin was estimated using ELISA while an automatic blood chemical analyzer was employed for the measurement of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Malondialdehyde (MDA), glutathione reduced (GSH) and superoxide dismutase (SOD) were measured using previously described standard methods. For these measurements, blood sample was obtained at once by retro-orbital bleeding under anaesthesia with pentobarbital (50 mg/kg; I.P.). Data were expressed as mean±SEM, compared by ANOVA. HSD rats showed reduced glucose tolerance (AUC: 2016.8±119.2 vs. 1017.5±59.9, p<0.05) and insulin sensitivity (AUC: 535.88±36.41 vs. 414.5±29.08, p<0.05) when compared with ND rats but intra-gastric administration of coffee prevented these metabolic abnormalities in HSD+COF (AUCOGTT: 1132.3±64.5; AUCITT: 388.75±26.27). In addition, insulin concentration was markedly increased in HSD rats compared with ND rats (12.25±0.51 vs. 7.69±0.22, p<0.05), but was suppressed in HSD+COF rat treated with coffee (9.21±0.66, p<0.05). Whereas compared with the HSD rats, the levels of TG and LDL (0.44±0.06 vs. 1.43±0.32; 0.75±0.03 vs. 0.91±0.06 respectively, p<0.05) decreased; HDL (1.10±0.06 vs. 0.69±0.02, p<0.05) increased significantly in HSD+COF rats. Additionally, MDA level was reduced (21.4±2.36 vs. 37.4±3.59, p<0.05), GSH (0.53±0.03 vs. 0.24±0.01, p<0.05) and SOD (4.38±0.47 vs. 1.63±0.01, p<0.05) activities were increased in HSD+COF when compared with HSD rats. Collectively, our data indicate that coffee consumption confers protection against the risk of contracting non-insulin dependent diabetes in rats and lends support to the idea that coffee consumption is associated with a lower risk of type 2 diabetes. Understanding some aspect of the relationship between coffee and diabetes is a desirable step in the context of healthy eating habits and disease control.