Objective: Based on our previous findings that, reflecting mild inflammation, the exposed facial skin shows much poorer functional properties of the stratum corneum (SC) in the dry and cold winter than those evaluated in the same individuals in the warm and humid summer time, we conducted a half-side test on the face to determine how the facial skin changes induced by a winter environment are improved by daily applications of a moisturizing cream as assessed by non-invasive biophysical and cytological methods. Methods: One side of the face of 16 young females was treated with a moisturizing cream twice daily for 6 weeks, with the other side serving as the non-treated control. Before treatment, 3 and 6 weeks after the start of the treatment, high-frequency conductance as a parameter of the skin surface hydration, transepidermal water loss (TEWL), a parameter of the water barrier function of the skin, and the skin surface lipid level were measured on the cheeks. Obtaining the SC from the skin surface by adhesive tape, interleukin (IL) 1α and IL-1 receptor antagonist (IL-1ra) in the SC and cornified envelope (CE) maturation were determined. Results: At first, baseline measurements conducted before treatment showed rather high TEWL values suggestive of an impaired skin barrier. During the treatment with the moisturizing cream, significantly higher conductance values and lower TEWL values were found on the moisturizer-treated side, accompanied by a decreasing IL-1ra/IL-1α ratio and immature CEs. Conclusion: These results suggested that the daily application of a moisturizing cream is effective in improving mild subclinical inflammation that is induced on the facial skin by the winter environment.