Introduction The decision to start insulin therapy is often difficult. Determining the barriers against insulin therapy initiation can facilitate care and treatment strategies. The aim of this study was to evaluate the barriers against initiating insulin therapy among patients with diabetes living in Yazd, Iran. Methods This descriptive study was conducted on 214 patients referred to the Diabetes Center of Yazd University of Medical Sciences in 2015. Participants were randomly selected, and then they completed the insulin noncompliance questionnaire (20 questions). The percentage of adherence and the factors contributing to nonadherence to insulin therapy were analyzed using descriptive statistics, the Kruskal–Wallis test, and the Mann–Whitney test. Results The most prevalent reason for insulin therapy refusal was expecting a new method of diabetes treatment (54.7%), followed by requiring someone else to administer the injection (19.2%), fear of needles, cost, traveling (18.7%), and stress/emotional problems (18.2%). Lack of trust in the physician was the least restrictive reason for nonadherence to insulin therapy. Conclusion The most common reason given for insulin therapy refusal was the lack of adequate education. Therefore, specialized educational interventions can help minimize barriers and improve patients’ outcomes.