Endocannabinoids effectively regulate cell functions in all types of excitable tissues. Besides recent immunohystochemicall experements showed expression of cannabinoid receptors (both CB1 and CB2 types) in salivary cells (Prestifilippo JP et al., 2006). However physiological role of these receptors in unexcitable salivary cells remains unclear. Experiments were performed on male Wistar rats (6-7 weeks old, 130-160 g). The rats were anesthetized with i.p. injection of pentobarbital (30-40 mg/kg) Saliva was collected using variable speed peristaltic pump after intraglandular injection of agonist (50 μl). Ca2+ concentration in the secreted saliva was measured using Arsenazo III dye. Saliva protein content was determined using Lowry method. Submandibular acinar cells were isolated by collagenase digestion. In vitro total Ca2+ content in gland acinar cells was measured using Arsenazo III and expressed in nM Ca2+ per μg of protein. We showed that activation of both CB1 and CB2 types of cannabinoid receptors are involved in salivary cells physiology and contributed to the regulation of submandibular salivary gland function. Activation of cannabinoid receptors in the acinar cells of submandibular salivary gland with agonist of both CB1 and CB2 types of cannabinoid receptors – WIN 55,212-2 (5 μM), CB1 cannabinoid receptor`s agonist – (R)-(+)-Methanandamide (5 μM) and CB2 cannabinoid receptor`s agonist – virodhamine (30 μM) leads to the inhibition of resting saliva flow on 46 ± 8 % (p<0,01, n=8), 22 ± 8 % (p<0,05, n=6) and 31 ± 6 % (p<0,01, n=7) accordingly, compare to control and alteration in electrolyte saliva content. We showed that in vitro application of WIN 55,212-2, (R)-(+)-Methanandamide and virodhamine to the isolated acinar cells in Ca2+-free extracellular solution (1 mM EGTA, 5 min) decreased total calcium content on 39 ± 6 % (p<0,01, n=6), 21 ± 4 % (p<0,01, n=5) and 28 ± 4 % (p<0,01, n=8) correspondingly, compare to control. Whereas WIN 55,212-2 and virodhamine applied to isolated acini in the presence of SERCA inhibitor – thapsigargin (0,1 μM) in Ca2+-free medium (1 mM EGTA, 10 min) caused decrease in total cellular calcium content on 30 ± 6 % (p<0,05, n=8) and 19 ± 3 % (p<0,01, n=8) accordingly compare to the effect of thapsigargin only. The latter suggest the potentiation of the Ca2+ release from the ER upon activation of CB receptors. In such conditions (R)-(+)-Methanandamide (5 μM) didn`t evoke statistical significant changes in total cellular calcium content. Notable, we found that endocannabinoids significantly potentiate store-operated Ca2+ entry into the acinar cells. We suggested that observed changes in salivation can be caused by endocannabinoids-induced modulation of Ca2+ release from the endoplasmic reticulum and consequent store-operated Ca2+-entry.