Aim - Effects of homeopathic treatment with Hypericum perforatum (Hypericum) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model.Methods - Fifty-four male healthy White Wistar rats were divided into three experimental groups (n = 18), randomly: Sham-operation (Sham), control: silicon tube (Sil) and treatment: silicon tube + Hypericum (Sil/Hypericum). In the Sham group after anesthesia left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the Sil group the left sciatic nerve was exposed the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone tube. In the Sil/Hypericum group a silicone tube was implanted the same way and each animal received three oral drops of Hypericum 30c twice daily for 1 week. Each group was subdivided into three subgroups of six animals each studied 4, 8, 12 weeks after surgery.Results - Data were analyzed statistically by factorial analysis of variance (ANOVA) and, the Bonferroni test for pair-wise comparisons. Functional study showed faster and better recovery of regenerated axons in Sil/Hypericum than in Sil group (P < 0.05). Gastrocnemius muscle mass in Sil/Hypericum was significantly greater than in Sil group. Morphometric indices of regenerated fibers showed number and diameter of the myelinated fibers in Sil/Hypericum were significantly higher than in control group. Immunohistochemistry, showed the location of reactions to S-100 in Sil/Hypericum was clearly more positive than in Sil group.Conclusion - Hypericum improves functional recovery of peripheral nerve regeneration in rats.