Exercise training or chronic treatment with angiotensin-converting enzyme (ACE) inhibitors can ameliorate glucose intolerance, insulin resistance of muscle glucose metabolism, and dyslipidemia associated with the obese Zucker rat. The purpose of the present study was to determine the interactions of exercise training and ACE inhibition (trandolapril) on these parameters in the obese Zucker rat. Animals were assigned to a sedentary control, a trandolapril-treated (1 mg. kg-1. day-1 for 6 wk), an exercise-trained (treadmill running for 6 wk), or a combined trandolapril-treated and exercise-trained group. Exercise training, alone or with trandolapril, significantly (P < 0. 05) increased peak O2 consumption by 31-34%. Similar decreases in fasting plasma insulin (34%) and free fatty acids (31%) occurred with exercise training alone or in combination with trandolapril. Compared with control, exercise training or trandolapril alone caused smaller areas under the curve (AUC) for glucose (12-14%) and insulin (28-33%) during an oral glucose tolerance test. The largest decreases in the glucose AUC (40%) and insulin AUC (53%) were observed in the combined group. Similarly, whereas exercise training or trandolapril alone improved maximally activated insulin-stimulated glucose transport in isolated epitrochlearis (26-34%) or soleus (39-41%) muscles, the greatest improvements in insulin action (67 and 107%, respectively) were seen in the combined group and were associated with similarly enhanced muscle GLUT-4 protein and total hexokinase levels. In conclusion, these results indicate combined exercise training and ACE inhibition improve oral glucose tolerance and insulin-stimulated muscle glucose transport to a greater extent than does either intervention alone.