Cannabinoid receptors (CBRs) belong to G protein-coupled receptor superfamily. CBRs expression was suggested for the submandibular cells however their role in the acinar cell physiology remains unclear. Experiments were performed on male Wistar rats. The rats were anesthetized with i.p. injection of pentobarbital (30-40 mg/kg). Saliva was collected using variable speed peristaltic pump. The effectiveness of basal salivation was evaluated by saliva flow rate, concentration of total proteins, α-amylase activity and concentration of electrolytes (Ca2+, Na+, K+, P) in saliva collected from the ducts in oral cavity before and after administration of cannabinoids. Submandibular cells were isolated by collagenase digestion. In vitro we measured Na+/K+-ATPase activity in the submandibular acinar cell`s microsomal fraction. We showed that activation in vivo of CB1R and CB2R of submandibular salivary gland with selective agonist WIN 55212-2 (5 μM) caused suppression of basal salivation and alteration of saliva content. Similar changes were observed after single administration of cannabinoid and in the conditions of prolonged drug use. Maximal inhibition of basal salivation we observed in 10 min after single application of WIN 55212-2 (~ 45%) and ~ 60% – in the conditions of prolonged administration of an agonist. Prolonged treatment with WIN 55212-2 leads to acidification of secreted saliva (by 0,5-0,8 pH u). Any significant changes of K+, Na+, P concentrations in final saliva were observed upon activation of CBRs. Repetitive application of WIN 55212-2 also induced an increase of both calcium and proteins concentrations in saliva. An increase of total protein concentration began at 10 min (52 ± 9% of saline-treated group; n = 10, p < 0.05) and was increased for all period tested (72 ± 9% of saline-treated group at 15 min; n = 9, p < 0.05); α-amylase activity was increased by 25 ± 5 %, p < 0.05, n = 12. A significant increase of calcium concentration began at 20 min (47 ± 5% of saline-treated group; n = 8, p < 0.05) and lasted for 30 min during a repetitive WIN 55,212-2 application. We also showed that decrease of basal salivation is accompanied by inhibition of Na+/K+-ATPase activity (by 41 ± 6 %, p < 0.05, n = 7). Therefore upon activation of CBRs: i) the activity of cAMP-mediated signaling system that contribute to the protein secretion is increased; ii) transcellular H 2O transport that contribute to the fluid secretion is reduced forming the base of inhibition of basal salivation; iii) electrolyte saliva content remains unaltered suggesting an unaltered functioning of the ductal cells unlike acinar cells. Concluding, observed changes of saliva pH and Na+/K+-ATPase activity in acinar cells contribute to the CBRs-mediated inhibition of basal salivation by submandibular gland.