The zebrafish exhibits an enhanced capability of regenerating most of its adult tissues. In this study, we examine the roles of light illumination and functional expression of mitosis-specific gene wee1 on adult zebrafish caudal fin regeneration after amputation. During the first 3 days post-amputation (dpa), the caudal fin regenerate rapidly in the day but slowly at night when the fish are kept in a normal light-dark cycle (LD) condition. However, this day-night rhythm of fin regeneration is not seen when the fish are kept in constant dark (DD), constant light (LL), or in fish in which the circadian rhythms are disrupted by random light (RL) exposures. The rate of fin growth reaches the peak levels at 2.5 dpa in LD, but is delayed when the fish are kept in DD, LL or RL conditions. In zebrafish in which the expression of dpa is blocked by morpholinos, regeneration of the caudal fin is affected. Interestingly, the expression of dpa also displays robust circadian rhythms. Together, the data suggests that fin regeneration in zebrafish is regulated by both environmental cues and functional gene expressions. Alterations in lighting conditions or inhibition of wee1 expression result in decreases in fin regeneration after injury. (C) 2012 Elsevier Inc. All rights reserved.