Objective To investigate the effect of recombinant human endostatin on the expression of vascular endothelial growth factor (VEGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in hypertrophic scar (HS) of rabbit ears. Methods A total of 16 New Zealand rabbits were used to establish ear HS models. The model rabbits were evenly randomized into two groups: experimental group and control group. Rabbits in the experimental group were locally injected with recombinant human endostatin (0.1 mL, 5 mg/mL, every other day for five times) and those in the control group were injected with normal saline (0.1 mL, every other day for five times). The HS specimens were harvested 30 days after intervention and were grossly observed; RT-PCR was used to test the expression of VEGF and TIMP-1 mRNA, and TIMP-1 protein was examined by immunohistochemistry method. Results The mRNA expression levels of VEGF and TIMP-1 in experimental group were significantly lower than that in control group (VEGF: 0.279 0±0.030 7 vs 0.657 0±0.161 1, P<0.05; TIMP-1: 0.244 4±0.057 4 vs 0.730 2±0.103 8, P<0.05). The protein expression level of TIMP-1 in experimental group was significantly lower than those in control group (P<0.05). Conclusion Recombinant human endostatin can inhibit HS of rabbit ear, which might be through suppressing the expression of VEGF and TIMP-1.