Abstract Photobiomodulation (PBM) therapy is a continuously growing approach to stimulating healing and reducing inflammation and pain. However, its effects in the fields of regenerative medicine and tissue engineering are still under investigation. Studying PBM effects on the regenerative capacity of zebrafish can allow the application of novel clinical approaches where the impact of PBM will be cross‐linked with the stem‐cell therapeutic approaches. This study was done to establish an in‐vivo experimental setup for studying the effects of laser and ultraviolet therapy on zebrafish caudal‐fin regeneration and vascularization. Thirty zebrafish were randomly and equally allocated into three groups. The caudal‐fins of all zebrafish were amputated under anaesthesia. In the first control group, the caudal‐fin was only monitored until fully regenerated. In the second group, the amputated‐fin was irradiated with ultraviolet. Finally, in the third group, the amputated‐fin was irradiated with laser. Caudal‐fin regeneration and vascularization were assessed at days 0, 3, 6, 9, 12, and 15 in all fish. In terms of regeneration, the results indicated that it is possible to discriminate the regenerative effect of laser with the experimental setup as laser therapy showed a statistically significant difference when compared to control‐group. It was also found that regenerative stimulation of the group that received ultraviolet therapy showed significant difference when compared to the control group. In terms of vascularization, there was a statistically significant difference in all groups of the study, which may suggest that laser as well as ultraviolet have limited effects in terms of improving vascularization. This study presented a novel, simple and inexpensive method for the assessment of PBM effects on zebrafish. Laser and ultraviolet therapy appeared to act as regenerative stimulators for caudal‐fin regeneration of zebrafish. However, laser therapy results were, to some extent, better than ultraviolet therapy. This novel in‐vivo design of the experiment led to more rapid and reproducible results than in‐vitro experiments.