Objective To estimate the effect of tretinoin gel sheeting on early-stage hyperplastic scars in rabbit ears,and to evaluate the feasibility to prevent and treat hyperplastic scars with it.Methods The ears of 24 rabbits were used to establish a model of hyperplastic scar according to previously reported methods.Then,the rabbit ears were randomly divided into four groups:control group receiving no treatment,gel sheeting group treated with the vehicle of the tretinoin gel sheeting,0.05％ tretinoin group treated with 0.05％ tretinoin gel sheeting,0.1％ tretinoin group treated with 0.1％ tretinoin gel sheeting.All the gel sheetings were topically used twice daily for six consecutive weeks.During the treatment,the size,thickness,color and texture of scars were estimated.After six weeks of treatment,all the scar tissues were resected from the rabbit ears and subjected to hematoxylin and eosin (HE) staining and van Gieson (VG) staining.Statistical analysis was carried out by analysis of variance and rank sum test.Results The scars were deeply colored,thickened,hard and elevated with an uneven surface in the control group,but lightly colored,thinned and soft with the presence of small subcutaneous nodules in the other three groups.The surface of scars in the two tretinoin groups was similar to that of adjacent normal skin,and scaling was observed on the scar surface in the 0.1％ tretinoin group.HE and VG staining showed a disarrangement of collagen fibers with the formation of vortex-like structures in the control group.A significant decrease was noted in the number of fibroblasts and microvessels as well as amount of collagen deposition per unit cross-sectional area in the two tretinoin groups compared with the control group and gel sheeting group.Additionally,the collagen fibers were regularly arranged and parallel to the long axis of scars in the two tretinoin groups.The scar hyperplasia index (HI) was 3.173 ± 0.26,2.465 ± 0.19,1.906 ± 0.21 and 1.903 ± 0.23 in the control group,gel sheeting group,0.05％ tretinoin group and 0.1％ tretinoin group respectively,the fibroblast density (NA) was 5836.7 ± 527.03,4128.73 ± 387.66,3207.59 ± 439.17 and 3200.28 ± 421.48 respectively,and the area density of collagen fiber (AA) was 45.38 ± 5.83,36.57 ± 6.84,28.09 ± 3.82 and 28.07 ± 3.47 respectively.As far as HI,NA and AA were concerned,the control group differed significantly from the other three groups (all P ＜ 0.01),and the gel sheeting group from the two tretinoin groups (all P ＜ 0.01),but no significant difference was observed between the two tretinoin groups (all P ＞ 0.05).Conclusions Topical tretinoin gel sheeting can inhibit scar proliferation at early stage in rabbit ears,and may provide a new choice for the prevention and treatment of hyperplastic scars.