Background Rabies is very common in People's Republic of China. Henan province, in the central portion of China, is one of the most densely populated provinces in the entire country. With the new rabies epidemic trend noted in northern and western China, it is necessary to investigate the characteristics of human rabies in this area and control the disease.Methods We chose patients in hospital isolation in 18 municipalities in Henan province as the investigation subjects. Data were collected through systematic reporting from these hospitals, whereas a questionnaire was applied to the relatives of patients.Results A total of 1022 rabies cases were reported. The incidence of human rabies in Henan has increased rapidly since 2005, having peaked in 2007, and maintained a high level in the remaining years. The cases were found mainly in rural areas in the south and east of the province. Rabies was often noted in summer and with the highest number in August. Most cases were noted in males and often in farmers. The patients aged between 40 and 60 years accounted for 36.8 % of all the cases. The wound treatment rate (12.2 %) and vaccination rate (2.6 %) of rabies cases after exposure were relatively low, while the rabies immunoglobulin utilization rate was only 2.8 %.Conclusions Rabies epidemic cases at the county level overall were increasing in Henan province during the period of 2005-2013; the epidemic has spread quickly. The data in this study imply that the disease could be better managed by more integrated surveillance across human health and veterinary sectors, improved education and better government policies.(AU)