Poor secretion of transplanted submandibular glands (SMGs) during the latent period may cause duct obstruction and affects the surgical outcome. The objective of this study was to investigate the efficacy and systemic side effects of carbachol on transplanted SMG secretion. Twenty-seven patients who underwent SMG transplantation for severe keratoconjunctivitis sicca were treated with subcutaneous injections of 0.2 mg/2 ml carbachol at 10 days, 1 month, and/or 3 months after surgery. The effect on secretion was evaluated by Schirmer test and technetium 99m (Tc-99m) scintigraphy. Systemic side effects were evaluated subjectively using a questionnaire. The results showed that the time to onset varied from 4 to 9 min and the duration of action from 50 to 110 min after carbachol administration. The secretion at each time point after drug administration was significantly higher than the pre-administration value (all P < 0.01). Tc-99m scintigraphy showed a decline in the dynamic time activity curve in 26 patients, demonstrating a stimulatory effect on the secretion of carbachol. No serious systemic side effects were experienced. In conclusion, the intermittent administration of carbachol could be an effective and safe strategy to promote secretion from transplanted SMGs in the latent period to prevent duct obstruction.