Background The most prominent nonneurological finding in the common compression neuropathy carpal tunnel syndrome (CTS) is fibrosis of the subsynovial connective tissue (SSCT). Recently, a rabbit model of CTS has been developed, based on the hypothesis that SSCT injury and subsequent fibrosis cause nerve compression. The purpose of this study was to evaluate the effects in this model at earlier and later time points than have heretofore been reported. Methods Sixty rabbits were operated on and observed at two different time periods: 6 and 24 weeks. Nerve electrophysiology (EP), SSCT histology, and SSCT mechanical properties were assessed. Results There was no significant difference in median motor nerve amplitude or latency at either time point. The total cell density in the SSCT was significantly higher at 6 and 24 weeks compared to controls. The mean size of the collagen fibrils in the SSCT was higher 6 and 24 weeks after surgery compared to controls. Both the ultimate load and the total energy absorption of the SSCT were significantly higher at 6 and 24 weeks compared to controls. Conclusions In this model, there were signs of SSCT fibrosis and histology changes at 6 weeks, which persist after 24 weeks. Thus, this model leads to sustained SSCT fibrosis, which is one characteristic of human CTS. However, no significant EP changes were found at these two time points, which is in contrast to the findings reported previously for this model at 12 weeks. The significance of the differences in EP findings will be the subject of future studies.