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Objective To determine the effects of weight-bearing (WB) versus nonweight-bearing (NWB) exercise for persons with diabetes mellitus (DM) and peripheral neuropathy (PN). Design Randomized controlled trial with evaluations at baseline and after intervention. Setting University-based physical therapy research clinic. Participants Participants with DM and PN (N=29) (mean age ± SD, 64.5±12.5y; mean body mass index [kg/m2] ± SD, 35.5±7.3) were randomly assigned to WB (n=15) and NWB (n=14) exercise groups. All participants (100%) completed the intervention and follow-up evaluations. Interventions Group-specific progressive balance, flexibility, strengthening, and aerobic exercise conducted sitting or lying (NWB) or standing and walking (WB) occurred 3 times a week for 12 weeks. Main Outcome Measures Measures included the 6-minute walk distance (6MWD) and daily step counts. Secondary outcome measures represented domains across the International Classification of Functioning, Disability and Health. Results The WB group showed greater gains than the NWB group over time on the 6MWD and average daily step count (P<.05). The mean and 95% confidence intervals (CIs) between-group difference over time was 29m (95% CI, 6–51) for the 6MWD and 1178 (95% CI, 150–2205) steps for the average daily step count. The NWB group showed greater improvements than the WB group over time in hemoglobin A1c values (P<.05). Conclusions The results of this study indicate the ability of this population with chronic disease to increase 6MWD and daily step count with a WB exercise program compared with an NWB exercise program.