Objective: To observe the changes in distribution and density of the nerve fibers in remnant splenic tissue after subtotal splenectomy for splenomegaly due to portal hypertension, so as to evaluate the value of this procedure. Methods: Thirteen patients with splenomegaly due to portal hypertension undergoing subtotal splenectomy with retroperitoneal transplantation of pedicled remnant spleen were selected. The specimens of splenomegaly tissues after surgical resection and the remnant splenic tissues from puncture biopsy 8 years after surgery in these patients were obtained, and specimens of splenic tissues harvested from 13 cases with splenic trauma served as normal control. The distributions and densities of splenic nerve fibers with positive neuropeptide Y (NPY) and neurofilament 200 (NF200) were detected by immunohistochemical staining. Results: The distributions of either NPY or NF200 positive nerve fibers were similar among the three groups of splenic tissues, but the splenomegaly tissue showed a relatively high density of both positive nerve fibers. Quantitative analysis within the red pulp of the spleen showed that the densities of both NPY and NF200 positive nerve fibers in splenomegaly tissue were significantly higher than those in remnant splenic tissue or normal splenic tissue (all P<0.05), but there was no significant difference between splenic tissue and normal splenic tissue (both P>0.05). Conclusion: After subtotal splenectomy, the distribution and density of nerve fibers in the remnant spleen are approximately the same as those in normal spleen, which suggests that the nerve function in the remnant spleen may gradually return to normal after elimination of the high pressure environment.