Most of organisms living on the earth have an internal clock which drives oscillations in physiology and behavior with a period of about 24 hours. We are not usually aware of this system. But when travelling rapidly through multiple time zones, it makes us aware of desynchrony in phase between our internal clock and external light-dark (LD) cycles. Although jet lag is recognized as a chronobiological problem, its specific molecular and cellular mechanisms are poorly understood. In screening candidate genes responsible for jet-lag, we generated V1a and V1b receptor double-knockout mice (V1a^-/-V1b^-/- mice), which were expressed in the suprachiasmatic nucleus (SCN). We found that locomotor activities in V1a^-/-V1b^-/- mice immediately re-entrained after phase shifts of LD cycles. We next examined the expression profiles of clock genes in the SCN under jet-lag condition. Before jet lag, circadian expressions of Per1 in the wildtype (WT) and V1a^-/-V1b^-/- SCN were quite similar. At ZT2 (ZT represents Zeitgeber time used in LD cycle; ZT0 is lights-on and ZT12 is lights-off), Per1 was seen in 'phase-leading' cells located in the periventricular part of the dorsomedial SCN. Per1 expressions were widely observed across the SCN at ZT6, while very few Per1-positive cells were found at ZT14-22. Whereas such a circadian expression pattern in Per1 gene was observed at day 3 in the V1a^-/-V1b^-/- SCN, characteristic Per1 expression rhythm was not found in WT mice at day3 after jet lag; phase-leading cells were not detected at ZT2 and modest amounts of Per1-positive cells were observed throughout the day 3. At day 9, circadian expression rhythm in Per1 gene appeared as it showed before jet lag in WT SCN. These results indicate that vasopressin-V1aV1b signaling in the SCN has a key role in jet lag, and highlight its potential importance as a therapeutic agent for management of circadian rhythm misalignment, such as jet lag.