The aim of this study was to analyze the role of vascular endothelial growth factor (VEGF) in mechanisms of cutaneous remodeling induced by fractional CO(2) laser treatment. The dorsal skin of Kunming mice was exposed to a single-pass fractional CO(2) laser treatment. Biopsies were taken 1 h, and 1, 3, 7, 14, 28 and 56 days after treatment. Skin samples VEGF expression was evaluated by immunohistochemistry and ELISA, fibroblasts by hematoxylin-eosin staining, and types I and III collagen by ELISA. Staining for VEGF was found in many types of cell including fibroblasts. The amount of VEGF in the skin of laser-treated areas had increased significantly compared to that in the control areas on days 1 and 3 (P < 0.05, P < 0.01, respectively), then decreased by day 7 after treatment and returned to the baseline level. The number of fibroblasts in the skin of the laser-treated areas had increased significantly compared to that in control areas on days 3, 7, 14, 28 and 56 after irradiation (P < 0.05, P < 0.01, P < 0.01, P < 0.01, P < 0.01, respectively). The amount of type I collagen was significantly higher in the skin of the laser-treated areas compared to that in control areas from day 28 to day 56 (P < 0.05, respectively), and type III collagen was significantly higher from day 3 to day 56 (P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01, respectively). There was a positive correlation between the level of VEGF and fibroblast proliferation early stage after laser treatment (r = 0.853, P < 0.01), but there was no correlation after the first week (r = -0.124, P > 0.05). The amounts of type I and III collagen showed no significant correlations with the expression of VEGF in the late stages after laser treatment (r = 0.417, P > 0.05 and r = 0.340, P > 0.05, respectively). The results suggest that VEGF might be mainly involved in the early stages of wound healing, including the stages of acute inflammation, fibroblast proliferation and vessel formation induced by fractional CO(2) laser resurfacing.