Acute photodamage is an acute inflammatory reaction of the skin after ultraviolet (UV) irradiation. Many drugs have been successfully used for the treatment and prevention of photodamage.To evaluate the molecular mechanism of N-terminal 5-mer peptide analog P165 of amyloid precursor protein in repairing photodamaged rat skin.We establish a rat model of acute UVB photodamage. The ratskin was treated with or without 250, 500, and, 1000 μM P165. Histological analysis was performed by hematoxylin and eosin staining. Apoptotic cells were analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The kits were used to measure the levels of protein carbonyl (PC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH). Western blotting was used to measure Nrf2.P165 repaired UVB-induced cutaneous erythema and edema, and reduced apoptosis of skin cells. The levels of PC, MDA, and 8-OHdG in 250 and 500 μM P165 groups were all lower than those in the solvent group. Activities of SOD, CAT, and GPx, and the level of GSH in P165 groups were higher than those in the solvent group. Nrf2 expression in the solvent group was higher than that in the negative group, whereas in the 500 μM P165 group was higher than in the solvent group.Our findings suggest that P165 repairs the rat skin with acute photodamage by reducing oxidative stress. These activities may be mediated by promoting the Nrf2 signaling pathway. Thus, P165 may be a promising agent for the treatment of acute photodamage, which may be used in cosmetics and postsun repair.Copyright: © 2021 Indian Journal of Dermatology.