Abstract: Objective To investigate the effect of prolonged axon depletion on senescence-associated beta galactosidase (SA-β-gal) expression in Schwann cells (SCs) of adult rats. Methods Male adult Sprague-Dawley (SD) rats were randomize grouped into sham-operated group and denervation groups for 1 week, 2 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks and 8 weeks. Rats were subjected to right sciatic nerve transection. After particular denervation duration for the distal stumps, animals were anesthetized and perfused. Proximal stumps of 5 mm and distal stumps of 10 mm from injured nerves, and the corresponding segments from the sham groups and contralateral nerves were harvested and prepared for SA-β-gal staining to detect SA-β-gal expression. Then, additional injured distal stumps denervated for 8 weeks were employed for determining cellular distribution of SA-β-gal expression by co-labeling of SA-β-gal and SC-specific protein (S100β). Results SA-β-gal expression transiently increased in distal tips of proximal stumps 2 weeks after adult rat sciatic nerve transection without suture. In contrast, in the distal stumps of transected adult rat sciatic nerves, axon depletion for 2 weeks increased SA-β-gal expression, and the increased expression of SA-β-gal remained constant after prolonged denervation durations. Furthermore, combination of SA-β-gal staining with S100β immunofluorescence staining showed that SA-β-gal expression was exclusively present in denervated SCs. Conclusion Prolonged axon depletion increased SA-β-gal expression in adult rat SCs.