Circadian rhythm plays a critical role in the progression of autoimmune diseases. While our previous study demonstrated the therapeutic effects of melatonin in experimental autoimmune uveitis, the involvement of circadian rhythm remained unclear. Using a light-induced circadian rhythm disruption model, we showed that disrupted circadian rhythms exacerbate autoimmune uveitis by impairing the stability and function of Treg cells. Mechanistically, we identified the core clock gene Per1, which is significantly reduced under circadian disruption, is essential for Treg cell metabolism and immunoregulatory function. This study underscores the pivotal role of circadian rhythm-related Treg cells in autoimmune disease progression.