Objective To examine the effect of a compound healthy ear agent (CHEA) from traditional Chinese medicine (TCM) on i) age-related apoptosis of cochlear hair cells (OHC) and spiral ganglion neurons ( SGN) using transmission electron microscopy (TEM), and on ii) localized expression of brain-derived neurotrophic factor (BDNF) and neuron-specific nuclear antigen (NeuN) to investigate mechanisms of CHEA actions. Methods Twenty-two C57BL/ 6J mice were randomly divided into two groups at 1 month of age. Eleven animals were provided tap water daily until 7 months of age; the age-related cochlear degeneration control group (7-month-old control group). Another 11 animals drank CHEA 1. 83 g / (kg·d) until 7 months of age; the TCM-treated group (7-month-old TCM group). Cochlea of euthanized animals were removed and processed into paraffin-embedded slices. Using TEM, ultrastructural changes were examined in the remaining and undisintegrated OHC and SGN associated with OHC at the basal region of cochlea from 7-month-control and 7-month-old TCM groups. Localized expression of BDNF and NeuN in SGN was observed by LCM combined with a morphological multi-overlap immunofluorescence technique, and examined using statistical analyses. Results In the 7- month-old control group, remaining and undisintegrated OHC and SGN associated with OHC in cochlea basal regions exhibited atrophied cytostomes, irregular nuclei and chromatin structure, texture structure presented vague, and high electron density; in particular, SGN were different in size and shape, significantly decreased in number, and exhibited nuclei chromatin that had disintegrated or dissolved to form vacuoles, representing the presence of apoptosis. However, the 7-month-old TCM group had no obvious apoptosis in OHC or SGN of basal cochlear regions, which exhibited more complete morphological structures and nuclei with a uniform chromatin distribution, texture structure presented clear, a lower electron density, and only individual nuclei had dissolved to form vacuoles. The localized expression levels of BDNF and NeuN in the basal cochlear region were higher (P < 0. 05) in the 7-month-old TCM versus the 7-month-control group. Conclusions Ultrastructural changes of nuclei and decreased expression of NeuN in cochlear OHC or SGN were important apoptotic features in aging cochlear neurocytes. Apoptosis in SGN was earlier than in OHC. The TCM reduced the ultrastructural changes in OHC or SGN, and increased NeuN expression in SGN, which suggests that TCM had a protective effect upon SGN, consistent with TEM observations. The mechanism of action may involve promotion of BDNF expression, which exerts a series of biological effects.