Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 (GLP-1), ghrelin and endomorphin-1 (EM-1) to the eastern and western style meals in patients with type 2 diabetes mellitus. Methods The study enrolled 57 patients with type 2 diabetes (20 men and 37 women, mean age (67.05±8.26) years). Eastern style meal (meal A) and western style meal (meal B) were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before (0 hour) and after (2 hours) each diet. Results The delta (2h-0h) of C- peptide in meal A was significantly lower than that in meal B (P=0.0004). C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A (P 〈0.0001, 〈0.0001, =0.001, =0.0004 respectively). Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A (P=0.0005, 0.0079 respectively). Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B (rA0h=0.7838, rB05=0.9368, rA25=0.7615, rB2h=0.9409, r A(2h-0h)=0.7531, rB(2h 05)=0.9980, respectively, P 〈0.0001). Conclusion Western style meal (high fat and protein food) could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones (GLP-1, ghrelin) and brain peptide (EM-1) at the first phase of digestion.