Pycnogenol® is a standardized extract of the bark of the French maritime pine, Pinus pinaster Ait., that has multiple biological effects, including antioxidant, anti-inflammatory and anticarcinogenic properties. This study describes the effect of topical application of lotions containing Pycnogenol® to Skh:hr hairless mice undergoing minimally inflammatory daily exposures to solar-simulated UV radiation (SSUV). We report that concentrations of Pycnogenol® of 0.05–0.2% applied to the irradiated dorsal skin immediately after exposure resulted in dose-dependent reduction of the inflammatory sunburn reaction, measured as its edema component. When mice received three consecutive daily exposures of minimally edematous SSUV, their ability to raise a contact hypersensitivity (CHS) reaction was suppressed by 54%. Pycnogenol® lotions applied postirradiation reduced this immunosuppression to 22% (0.05% Pycnogenol®) and 13% (0.1% Pycnogenol®). Furthermore, when CHS was suppressed by 71% with exogenous treatment with cis-urocanic acid, the putative epidermal mediator of photoimmunosuppression, 0.2% Pycnogenol® lotion reduced the immunosuppression to 18%. Chronic exposure to SSUV on 5 days/week for 10 weeks induced skin tumors from 11 weeks in both control mice and in mice receiving daily applications of 0.05% Pycnogenol®, but tumor appearance was significantly delayed until 20 weeks in mice receiving 0.2% Pycnogenol®. Furthermore, whereas 100% of control mice had at least one tumor by 30 weeks, and mice treated with 0.05% Pycnogenol® by 33 weeks, the maximum tumor prevalence in mice treated with 0.2% Pycnogenol® was significantly reduced to 85%, with some mice remaining tumor free. Average tumor multiplicity was also significantly reduced by 0.2% Pycnogenol®, from 5.2 in control mice to 3.5 at 35 weeks. Thus, topical Pycnogenol® offered significant and dose-dependent protection from SSUV-induced acute inflammation, immunosuppression and carcinogenesis, when applied to the skin after daily irradiation. Pycnogenol®, therefore, in addition to its recognized health benefits in other organs, appears to have potential in providing photoprotection for humans in a complementary role with sunscreens, having demonstrable activity when applied to the skin after, rather than before, UV exposure.