The conditions of impaired wound healing in the elderly female due to estrogen deficiency are associated with substantial morbidity and mortality and impose a significant monetary burden upon the world’s health services. The present work demonstrated that selective estrogen receptor modulator (Tamoxifen) produced histological effects on skin wound healing. At the 5th day after wounding, tamoxifen was seemed to accelerate proliferative phase by prompting re-epithelialization, decreasing wound gap and early scab disappearance in the epidermis. In the dermis it early finished the inflammatory phase by decreasing the number of the inflammatory cells specially the macrophages, this might be due to tamoxifen inhibitory effect on wound expression of proinflammatory cytokines as macrophages migration inhibitory factor (MIF). It also prompted the proliferative phase in the dermis by stimulating fibroplasia, angiogenesis and wound contraction. Moreover, it encouraged remodeling phase by decreasing the area of the granulation tissue, enhancing formation of new skin appendages and stimulating collagen synthesis. Those effects might be due to tamoxifen ability to induce the activity of transformation growth factor β1, which is a chemotactic for macrophages, mitogenic for fibroblasts and stimulant for collagen synthesis and angiogenesis. Also, tamoxifen stimulated estrogen receptors (Ers) of the epidermis to produce its estrogenic effects. Moreover, tamoxifen induced keratinocytes expressing Erβ protein and decreased the number of the lymphocytes by its antiproliferative effect on lymphocytes and its inhibitory effect on P-glycoprotein which is responsible for transmembrane transport of cytokines in lymphocytes.