Topical treatment of resistant psoriatic plaque stage lesions may be difficult and the systemic therapies seem inappropriate. Therefore, a topical 0.1% methylene blue (MB) hydrogel was prepared and evaluated for percent drug content, drug uniformity, pH, rheological and organoleptic characters such as feel tackiness, grittiness sensation, and transparency in addition to release kinetics study in vitro. The efficiency of the photodynamic therapy (PDT) of MB photo-activated using 565 mW Light emitting diode (LED) 670 nm was evaluated in patients with resistant plaque psoriasis. The gel was evaluated in single blinded study. The patients were subjected to repeated sessions of irradiation, skin biopsies from each patient in the beginning and at the end of the sessions were taken for histopathological studies. Results showed the hydrogel was transparent nongritty and the drug uniformly dispersed with pH=7.2 and viscosity value=25.04 Pa. The drug content was found to be 99.4 +/- 0.15 %. Drug release was following zero order kinetics with rate constant K=0.348 +/- 0.01 and T(1/2) = 0.95 +/- 0.5 hours. Sixteen patients experienced complete clearance of their treated lesions. Skin appeared normal in color, texture, and pliability with no complications indicating the lack of skin sensitivity. Histopathological examinations showed nearly normal epidermis at the end of all sessions. The authors concluded that the prepared hydrogel was safe, stable, and very effective. The results are encouraging to accept MB as a photosensitizer for PDT and as a safe and effective method for treatment of selected cases of resistant localized psoriasis