Based on the high prevalence and undiagnosed rate of diabetes mellitus in China in recent years, the aim of this work was to evaluate the availability, price and affordability of pharmacotherapy for diabetes in public hospitals in Hubei province, China. In 2016, a cross-sectional survey was conducted using World Health Organization/Health Action International (WHO/HAI) methodology. Information on the availability and prices of 20 antidiabetic drugs was collected from 34 public hospitals representing three levels of care. Of the 20 antidiabetic drugs, 70.6% were below 50% availability. Total availability of the 20 drugs was higher in secondary and tertiary hospitals than in primary hospitals. All three hospital levels had higher availability of essential than non-essential antidiabetic medicines. The median markup ratios of originator brands (OBs) and lowest-price generics (LPGs) were 15.6% and 2.1%, respectively. The median potential saving ratio of using generics was 31.3%. Overall, the median affordability of 31 antidiabetic drugs ranged from 1.2 to 8.5 days of disposable income for residents with three income levels. After insurance reimbursement, the increase in the proportion of affordable drugs in urban and rural areas averaged 35.5% and 12.9%, respectively. The proportion of drugs with low availability and low affordability dropped from 54.8% to 38.7%. However, 41.7% of urban diabetic patients and 74.0% of rural diabetic patients remained unable to afford the drugs surveyed. Higher income and generic substitution are factors facilitating affordability. In Hubei province, the overall availability of 20 antidiabetic drugs was low, especially in primary hospitals. The affordability of most drugs surveyed was also low. Current health insurance can greatly improve affordability for urban residents with middle or high income. Policy changes should focus on the supply, pricing and clinical use of antidiabetic drugs and special health insurance plan for low income population with diabetes.