Striae distensae is a challenging cosmetic problem for which various treatment modalities have been applied. To compare between the efficacy and tolerability of intradermal injection of autologous platelet-rich plasma (PRP) vs. microdermabrasion in the treatment of striae distensae. Sixty-eight patients with striae distensae were randomly assigned to three groups according to therapeutic modalities. Patients of group I were treated by intradermal injection of PRP alone, patients of group II were treated with microdermabrasion alone, and patients of group III were treated with combination of intradermal PRP and microdermabrasion in the same session. Each patient underwent maximum of six sessions at 2-week interval. Skin biopsies were taken from some patients at baseline, and 3 months after the last sessions stained with hematoxylin and eosin stain, Masson trichrome, orceun, and Van Gieson stains to study of histopathological changes and efficacy of treatment. There was significant clinical improvement of striae distensae in patients treated with PRP injection and patients treated with combination of PRP and microdermabrasion when compared with patients treated with microdermabrasion. However, combination of PRP and microdermabrasion in the same session showed better results in short duration. Collagen and elastic fibers were markedly increased in the dermis at the end of treatment sessions. Platelet-rich plasma alone is more effective than microdermabrasion alone in the treatment of striae distensae, but it is better to use the combination of both for more and rapid efficacy. However, each one of them is well tolerated by the patients, safe and cost effective.