Intro: This study will investigate the safety and efficacy of using timolol, a non-selective beta adrenergic antagonist (BAA), topically to treat diabetic foot ulcers. We hypothesize that topical timolol is more effective in achieving wound closure than using the standard of care (SOC) treatment for diabetic foot ulcers, and is a safe therapeutic alternative. Research Design/Methods: The study is a Phase 2 randomized, double blinded, controlled and parallel-group clinical trial with 2 treatment arms, receiving either the SOC plus topical Timoptic-XE® or a control group receiving SOC plus a non biologically active gel (hydrogel, as placebo medicine). The study population will be selected from the VA Northern California Health Care System, Veterans who present with diabetic foot ulcers. We will require 24 subjects enrolled in each treatment arm, for a total of 48 sample size to provide a power of 80% to detect a 43 % difference, with 63% healing in the timolol group and 20% with the standard of care, at a significance level 0.05 and an overall attrition will be 35%. We will perform simple allocation of the subjects using an electronic randomization for treatment assignment. Following recruitment, patients that have met the eligibility criteria and signed an informed consent, will then undergo two weeks of baseline screening to screen out rapid healers. Next, the patient will be randomly assigned treatment, with unique identifiers assigned, with subject and investigator blinded as to treatment. Subjects will topically apply daily either the treatment medication or the placebo on the foot ulcer for 12 weeks, or until healed, whichever comes first. Measurements of wound size and other data will be collected at baseline, followed by weekly visits for 12 weeks, and then a follow-up period. The maximum study duration for any subject is 31 weeks with 3 phases (two weeks in the Screening Phase, up to 12 weeks in the Active Phase including a confirmatory visit, followed by a second confirmatory visit a week later, and one month and three-month in the Follow-Up Phase). Analysis: The primary end point of wound closure (skin re-epithelialization without drainage or dressing requirements) at 12 weeks will be analyzed using the two-sided Fisher's exact test. Secondary outcomes such as the rate of ulcer healing by the 12th week of care, time to achieve complete ulcer closure, recidivism, occurrence of adverse events will be analyzed with p- value adjustments. A two-way ANOVA with a post hoc test will be used to relate timolol serum levels to wound healing. The analysis of the wound characteristics, the subjects' characteristics, and the safety parameters will be performed using logistic regression. Subjects will complete the Veterans Rand (VR-36) Health Survey to evaluate quality of life, the Lower Extremity Functional Scale, which will be analyzed along with the Charlson co-morbidity index, using ANCOVA.