Exposure of skin to solar UV radiation induces oxidative stress and suppression of cell-mediated immune responses. These effects are associated with the greater risk of several skin disorders including photoaging and photocarcinogenesis. We have shown that UV-induced infiltrating leukocytes contribute in developing oxidative stress in UV-irradiated skin. The peak period of UV-induced infiltrating leukocytes lies between 48 and 72 h after UV exposure of the skin. In this study we demonstrated that UV (90 mJ/cm²)-induced infiltrating CD11b cells in C3H/HeN mice skin were the major source of oxidative stress. Hydrogen peroxide (H₂O₂) was determined as a marker of oxidative stress. Flow cytometric analysis of viable cells revealed that the number of CD11b H₂O₂ cells were significantly higher (31.8%, P < 0.001) in UV-irradiated skin in comparison with non–UV-exposed skin (0.4%). Intraperitoneal administration of monoclonal antibodies to CD11b (rat IgG2b) to C3H/HeN mice inhibited UVB-induced infiltration of leukocytes, as evidenced by reduction in myeloperoxidase activity (64–80%, P < 0.0005), concomitant with significant reduction in H₂O₂ production both in epidermis and dermis (66–83%, P < 0.001–0.0005) when compared with the administration of rat IgG2b isotype of anti-CD11b. Furthermore, CD11b and CD11b− cell subsets were separated by immunomagnetic cell isolation technique from total epidermal and dermal single cell suspensions obtained 48 h after UV irradiation of the skin and analyzed for H₂O₂ production. Analytical data revealed that CD11b cell population from UV-irradiated skin resulted in significantly higher production of total H₂O₂ in both epidermis and dermis (87–89%, P < 0.0001) in comparison with CD11b− cell population (11–13% of total H₂O₂). These data revealed that infiltrating CD11b cells were the major source of oxidative stress in UV-irradiated skin and thus may contribute to photoaging and promotion of skin tumor growth within the UV-irradiated skin. Together, these data suggest that reduction in UV-induced skin infiltration of CD11b cells may be an alternative and effective strategy to reduce solar UV light–induced oxidative stress–mediated skin disorders including photoaging and photocarcinogenesis.