The use of fractional CO2 laser and pulsed dye laser (PDL) therapy to treat and/or prevent scarring following burn injury is becoming more widespread with a number of studies reporting reduction in scar erythema and pruritus following treatment with lasers. The objective of this study was to directly compare the efficacy of PDL, fractional CO2 , and PDL and fractional CO2 laser therapy in immature red hypertrophic scars in a standardized animal model. Ten New Zealand big-eared rabbits were used to make rabbit ear hypertrophic scar models. A total of 80hypertrophic scar models were obtained and randomly divided into groups: control (Group A), Fractional CO2 laser (Group B), pulse dye laser (Group C), combined (Group D), 20 in each group. Wound sites were treated with PDL, Fractional CO2 laser, or both at 28days post-grafting. Grafts receiving no laser therapy served as controls. Hypertrophic scar appearance, morphology, size, and erythema were assessed, and punch biopsies were collected. At days 7 and 28, additional tissue was collected for biomechanical analyses and markers for HE staining, Masson staining, immunohistochemical method to determine the CD31 content in the scar; Western blot to detect the expression of VEGF protein in scars. After the day 7 and 28, the scars were collected. Histomorphological change in scars was observed by hematoxylin-eosin staining, Masson staining. The expression of CD31, VEGF protein, and the cell apoptosis rate was detected by immunohistochemical method. (i) In morphological observation, HE staining and Masson staining, both the number of fibroblasts and amount of collagen fibrils in the experimental group were significantly reduced compared with those in control group. (ii) Micro-vessel Density (MVD) value can be found much smaller in the experimental groups than the control (p<0.05). Among the four experimental groups, there was a significant difference among 14d, 21d, and 28d groups (p<0.05). (iii) On days 7 and 28 after treatment, expression of VEGF could be regulated in experimental group (p<0.05). Among the three experimental groups, the decrease of VEGF in the combined group was significantly stronger than that of the other two. The effect of Fractional CO2 laser combined with pulsed dye laser treatment was shown to be better than that of Fractional CO2 laser or pulsed dye laser alone and inhibits the early hypertrophic scar in rabbit ears.