In this single-blind, parallel, placebo-controlled study, the pharmacokinetics, pharmacodynamics, tolerability, and safety of subcutaneous exenatide were evaluated in 40 Japanese patients with type 2 diabetes. Patients were allocated to 4 groups and randomized to receive exenatide (n = 8/group) or placebo (n = 2/group), with all receiving placebo on day 1. On day 2, patients received single-dose exenatide (2.5 μg [group A] or 5 μg [groups B, C, and D]) or placebo and then bid on days 3 to 5. On days 6 to 10, groups A and B continued on 2.5 and 5 μg bid; groups C and D received 10 and 15 μg bid, respectively. The last dose was given on the morning of day 10. All adverse events were mild or moderate in severity. Exenatide was generally well tolerated up to 10 μg. Exenatide was well absorbed with a median tmax of 1.5 hours and mean t1/2 of 1.6 hours; exposure increased with dose. Up to 10 μg, exenatide reduced postprandial glucose concentrations in a dose-dependent fashion compared with placebo; decreases were similar for 10 and 15 μg. An Emax model demonstrated that doses higher than 2.5 μg were necessary for adequate glycemic response. Based on tolerability and pharmacokinetic/pharmacodynamic relationships, 5 and 10 μg exenatide may be considered for further clinical development in Japanese patients with type 2 diabetes.