Objective To analyze the epidemic characteristics and causes of post-exposure immunization failure of rabies in Hubei Province from 2015 to 2021, and to provide evidence for the prevention and control of rabies in Hubei Province. Methods The investigation data of rabies cases in Hubei Province from 2015 to 2021 were collected, and descriptive epidemiological methods were used for data analysis. Results A total of 127 cases of rabies were reported in Hubei Province from 2015 to 2021, with an average annual incidence of 0.31/million, showing a downward trend. The male to female ratio was 1.70:1. Farmers accounted for 82.67% of the total cases, and the 50-79 years old group accounted for 75.59%. The incidence was mainly concentrated in Xiangyang, Shiyan, Yichang and Jingmen, accounting for 77.17%. Most of the cases were concentrated in summer and autumn. Exposure of grade Ⅱand Ⅲ accounted for 24.79% and 75.21%, respectively. Hands, lower limbs below knee, head, arms and lower limbs above knee accounted for 46.15%, 25.21%, 9.40%, 8.55% and 7.69% of the exposed parts, respectively. Dogs, cats and wild animals accounted for 95.73%, 3.42% and 0.85% of the exposed animals, respectively. Stray animals, domesticated animals, neighbors' animals and wild animals accounted for 41.88%, 37.61%, 19.66% and 0.85% of animal sources, respectively. Neither the neighbors’ animals nor domesticated animals were vaccinated against veterinary rabies virus. After exposure, 8.55% of patients went to medical institutions for standard treatment of wounds, 9.40% were vaccinated with human rabies vaccine, and 4.55% of patients with grade III exposure were injected with rabies virus immunoglobulin. The incubation period within 6 months, from 6 months to 1 year, and over 1 year accounted for 72.22%, 14.74%, and 12.04%, respectively. The exposure degree (Z=-1.98, P < 0.05), exposure site (χ²=10.91, P < 0.05) and wound treatment (χ²=15.73, P < 0.05) had statistically significant effects on the incubation period. Among the 11 cases of post-exposure immunization failure, all were grade Ⅲ exposure, 63.63% were exposed to the head and face, 81.81% were not fully vaccinated with human rabies virus vaccine, 63.63% were not immunized with immunoglobulin, and 27.27% were inappropriate wound treatment. Conclusion The key to rabies prevention and control is to standardize dog management, strengthen rabies education, standardize post-exposure wound treatment, timely vaccinate against rabies virus, and inject rabies virus immunoglobulin when necessary.