Intravenous infusion of acetylcholine (ACh) caused Ca²⁺oscillations synchronized at the tissue level in rat submandibular gland (SMG). To examine the mechanism of the synchronized Ca²⁺oscillations in SMG, we monitored Ca²⁺responses and blood flows (BF) in live animals using the intravital Ca²⁺imaging system and the laser speckle BF imager. Monitoring of BF dynamics demonstrated that ACh caused oscillatory changes in BF in SMG. The oscillatory changes in BF showed a diverse spacial patterns occurring from anterior, intermediate, lateral, and posterior regions of SMG. Preadministration of calciumantagonist, nicardipine, an angiotensin II (Ang II) receptor blocker, irbesartan, or an angiotensin converting enzyme inhibitor, enalapril (Ena), changed the BF oscillations to a sustained increase in BF without fluctuation. After the attenuation of BF fluctuation by Ena, intravenous infusion of Ang II recovered BF oscillation. Theseresults indicate that vasoconstriction by Ang II plays a critical role in the regulation of BF oscillations. In addition, BF oscillation do not require fluctuations ACh and Ang II concentrations in the plasma. Furthermore, simultaneous monitoring of Ca²⁺and BF dynamics in SMG revealed that the increase in intracellular Ca²⁺concentration preceded the increase in BF in most cases (85%, 71/84 oscillations, in 4 rats). These results suggest that Ca²⁺response of acinar cells leads vasodilation through the production of localized diffusible substances in the SMG.