Objective To study the inductive effect of targeted UVB phototherapy on skin hyperpigmentation and its mechanism.Methods Ten brownish guinea pigs were used to develop experimental models.After depilation,four adjacent areas were selected on the back of each guinea pigs and served as the control,low-dose,moderate-dose and high-dose group to receive targeted UVB irradiation with a cumulative dose of O,2500,3500,4500 mJ/cm2,respectively.After 6-week irradiation,the guinea pigs were sacrificed and skin sampies were obtained.The hyperpigmentation induced by UVB irradiation was estimated by naked eyes,staining for melanocytes(Imokawa method)and melanin granules(Masson-Fontana staining),respectively.Immunohistochemistry was carried out to determine the level of nitric oxide synthase and HE staining to observe epidermal histological changes.Results A statistical difference was observed in the pigmentation score,quantity of melanin granules and dopa-positive melanocyte number among the four groups (P<0.05),and the moderatedose group was higher than the high-dose group in terms of these parameters.The expression of inducible nitric oxide synthase increased in a radiation dose-dependent manner,and the median value for inducible nitric oxide synthase expression level was 0.50,1.25,1.75,2.00 in the control,low-dose,moderate-dose and highdose group,respectively(P<0.05).Conclusions Targeted UVB phototherapy can induce hyperpigmentation of the skin in brownish guinea pigs in a dose-dependent manner,but higher dose may not work better.To irradiate with an initial dose close to or slightly higher than the minimum erythema dose may result in a satisfactory effect with reduced cumulative dose and potential risk for cancer.