Introduction and hypothesis: New Zealand white rabbits are an inexpensive large-animal model. This study explored the rabbit as a model for mesh-augmented colpopexy using the intra-abdominal vagina. We hypothesized that polypropylene mesh would negatively impact rabbit vaginal smooth muscle (VSM) morphology and contractile function, similar to the nonhuman primate (NHP)—the established model for prolapse mesh evaluation. Methods: Restorelle was implanted onto the vagina of ten rabbits via lumbar colpopexy after a hysterectomy. Ten rabbits served as sham. Twelve weeks post-implantation, the vagina was excised and VSM morphology and vaginal contractility were assessed. Outcome measures were compared using independent samples t and Mann-Whitney U tests with a Bonferroni correction, where appropriate. Results from the rabbits were compared with published NHP data. Results: Animals had similar age, parity and BMI. VSM was 18% thinner after Restorelle implantation, P = 0.027. Vaginal contractility was 43% decreased in response to 120 mM KCl (P = 0.003), similar to the 46% reduction observed in the NHP vagina implanted with Restorelle (P = 0.027). Three meshes wrinkled in vivo, resulting in dramatic thinning of the underlying vagina in the area of the mesh causing a mesh exposure. Conclusions: Polypropylene mesh negatively impacts VSM morphology and vaginal contractility in the rabbit, similar to the NHP, suggesting that the rabbit may serve as an alternative large-animal model. The vaginal thinning and appearance of a mesh exposure in the area of a mesh wrinkle suggest the rabbit may also serve as a model for understanding the pathophysiology of mesh exposure.