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Skin cancer is the most common cancer in the world. Its main cause is chronic ultraviolet (UV) radiation exposure, responsible for initiation of DNA damage and cancer-enhancing inflammation. Relative to females, males are up to three times more likely to develop skin cancer and seventy percent more likely to die from it once affected. Our goal is to find causes of these significant sex differences. Given data from previous studies that demonstrates sex differences in the levels of inflammatory markers and immune cells, we hypothesize that sex differences in the inflammatory response to UV radiation is the causative factor of the sex differences in skin cancer. We showed that females demonstrated higher levels of inflammatory cytokines both in the skin and serum relative to males following chronic irradiation, and that they also have greater inflammatory edema and myeloperoxidase levels acutely, providing evidence of this inflammatory difference. We also show that circulating testosterone reduction from castration seems to play little role in these differences, while circulating estrogen reduction following ovariectomization results in lesser inflammation, correlating with a greater tumor burden in ovariectomized females from chronic studies in the context of our hypothesis.