Objective: To evaluate the efficacy of chitosan- methylene blue (MB) hydrogel mediated photodynamic therapy in the treatment of freckles. Patients and methods: Thirty four patients complaining from freckles were recruited in this Prospective, split-face controlled study. Pregnant women, patients with photosensitive dermatosis, other contraindications for phototherapy and use of topical or systemic retinoid treatment in the past 6 months were excluded. Chitosan hydrogel was prepared by dispersing 3g of chitosan in 2% acetic acid solution, and then MB added with continuous stirring until thoroughly mixed to prepare 0.01% MB-chitosan hydrogel. The left side of the face was treated by application of Chitosan- MB hydrogel, 30 min prior to treatments followed by irradiation with diode laser (650 nm wave lengths) twice weekly until complete clearance of the lesions or maximum 12 sessions. Improvement was graded as excellent (≥ 75%), very good (50–74%), Good (25–49%) and poor (< 25%). Results The release of MB from formulation follow first order kinetic model, MB content of the prepared hydrogel was found 99.51 % ± 1.1 of the claimed amount (0.01%w/w). Thirty four patients were enrolled in the study, the age of the patients ranged from 18-46 years and the duration of freckles ranged from 8 months to 17 years. Mean surface area, Density, Darkness and PSI score of freckles was significantly decreased in MB treated side compared with their baseline (P<0.05). Excellent improvement was occurred in 6 (17.6%) cases, very good improvement in 19(55.9%) cases, good improvement in 7 (20.6%) cases and poor improvement in 2 (5.9%) cases. Pain during treatment sessions was the most common complication followed by transient erythematic and post-inflammatory hyper pigmentation. Conclusions Chitosan- MB hydrogel mediated photodynamic therapy is an effective and safe method in the treatment of freckles