Keratoconjunctivitis sicca, characterized by reduction or lack of tears with the resulting consequences, is a relatively common disease. The current therapeutic options are largely symptomatic and insufficient in severe cases. During the last 10 years, 141 cases (150 eyes) of severe keratoconjunctivitis sicca have been treated by autologous submandibular gland transfer. It has been shown that autologous submandibular gland transfer is a lasting and effective solution for the severe cases. However, there are two main problems with this method that need to be resolved. One is that a lower flow rate leads to the obstruction of Wharton's duct in the early stage after transfer. The other is that half of the patients suffer from epiphora in the long term. In order to resolve the two problems, both clinical and basic research were performed to modify surgical procedures and to understand the mechanisms underlying the secretion of the transferred submandibular gland. We found that partial submandibular gland transfer could prevent or alleviate epiphora and that α1- and ß-adrenoceptors and vanilloid receptor 1 were involved in the secretion by normal and transferred submandibular glands. The agonists of these receptors could moderate structural injury and improve secretory function in the transferred submandibular gland. Keywords: keratoconjunctivitis sicca, dry eye syndrome, autologous submandibular gland transfer, receptor, surgery