Toxic heavy metals like mercury and cadmium are known to involve in altering the salivary flow so that can be appeared sialorrhea or ptyalism, the condition of increased salivary flow, or xerostomia (“dry mouth”), the condition related to inhibited or decreased salivary flow. Although many people were exposed to these heavy metal in work environment, dental clinics, the mechanism is rarely discussed in the clinical literature. The present study is to carried out analysis of AQP5 expression that play a key role in saliva fluid secretion and cell membrane water permeability on mercury- or cadmium-exposed mice submandibular gland. To investigate AQP 5 expression, immunohistochemical study and western blot assay were carried out on mercury- or cadmium-exposed mice. Additionally, RT-PCR, real- time PCR with specific primers were carried out. Cadmium or mercury exposure led ductal extension, ductal cell increase, and blood vessel increase in mouse submandibular gland. The mRNA and protein expression of AQP5 were increased in time dependent manners on cadmium or mercury exposed mouse. Also, AQP5 were translocated from basolateral membrane to apical membrane of acini cell. In conclusion, toxic heavy metal such as mercury and cadmium appear to alter the AQP5 expression and distribute to apical membrane of ductal cell and lead to alter salivary secretion.